Implant device and system for ablation of a vessel&#39;s wall from the inside

ABSTRACT

The current invention concerns systems, devices and methods for the ablation of a ablation of the wall of one or more pulmonary veins (PV) from the inside, preferably transmural ablation and preferably at the level of the antrum. Hereby, one or more implant devices can be implanted in the vessels and can subsequently be heated by external energy-providing means.

TECHNICAL FIELD

The invention pertains to the technical field of the treatment of bodilyvessels by means of ablation, more specifically to the treatment ofcardiac conditions such as atrial fibrillation (AF). In particular, thepresent invention relates to systems, devices and methods for theablation of a vessel's wall from the inside, more specifically toimplant devices and to the ablation of the wall of one or more pulmonaryveins (PV) from the inside, preferably transmural ablation andpreferably at the level of the antrum.

BACKGROUND

The present invention concerns a system of one or more implant devicesand excitation device, an implant device and a method using the systemand one or more devices for the treatment of arterial and venousstructures.

The present invention also concerns implant devices, a system of implantdevices and external excitation means, and a method for positioning oneor more implant devices in a vessel, and subsequently heating theseimplant devices, preferably simultaneously, thereby transferring heatfrom implant devices to the vessel's inner wall.

The system, device and method can for example be used for treatingatrial arrhythmias, more specific atrial fibrillation (AF), morespecific paroxysmal, persistent or permanent. More specifically thisinvention describes a method that allows to repeatedly create lesions inthe heart, more specifically in the atria, more specifically in the leftand right atrium, more specifically in the antrum or ostium of thepulmonary veins (PVs). Hereby, the general concept is to implant one ormore implant devices into the PVs or other vessels, said implant devicesmaking contact with the vessels' inner walls at the positions whereablation is deemed necessary in order to have PV isolation (PVI). Incontrast with prior art, ablation is not performed immediately, but theone or more implant devices can be heated up to a specified temperatureby external energy-providing means, which are spatially separated from,i.e. not touching, the implant device and able to provide energyremotely to the implant device for increasing the temperature of theablation region of the implant device up to an ablation temperature. Ina preferred embodiment, an implant device comprises an area which ismade from a material which may show magnetic hysteresis and the externalenergy-providing means are able to create a time-varying magnetic fieldat the position of the implanted device, hereby heating the implantthrough the phenomenon of magnetic hysteresis. The maximum temperaturethe implant device can reach, is limited by the Curie or Néeltemperature of the magnetic material used, above which temperature themagnetic hysteresis effect disappears. This Curie or Néel temperaturecan be engineered precisely to the necessary ablation temperature e.g.by changing the composition of the magnetic alloy that is used. Inanother embodiment, non-magnetic material may be used, and insulationmaterial may then be used to provide sufficient temperature-controllingmeans. In an embodiment, the heating of the implant device is done byJoule heating or direct heating, or any other heating system.

The implant device according to the present invention can thus be usedinside the heart, both the right and the left side, inside the pulmonaryveins, but also if necessary, in arterial and venous structures outsidethe heart.

The devices, systems and methods as described in this document may alsobe used in human or animal corpses or in models of human or animalbodies, e.g. for practicing or educational purposes, whereby the heatingof the implant devices leaves ablation marks on the vessel's inner wallwhich can be used to check if the implant devices were positionedcorrectly and sufficient ablation occurred.

The present document focuses its description on the application of thedevice inside the heart, both the right and the left side, and insidethe pulmonary veins.

A person skilled in the art will be able to interpret the device, thesystem and the method and to provide them of specific features,components or steps if to be used in other areas.

Human wellbeing is menaced by numerous disorders which change with time.The art of medicine continuously needs to innovate and to adapt to thesechanges. Despite incessant therapeutic improvements, cardiac diseaseremains the most important cause of death and hospitalizations in thewestern society.

Atrial fibrillation, often referred to as AF, is an arrhythmia of theheart causing irregular electrical activity, followed by disorganizedand ineffective contractions.

Patients experiencing AF suffer from palpitations, fatigue, severedecrease in quality of life, worsening of heart failure, cerebralstroke, increased mortality and many other symptoms.

Prevalence and incidence of AF is gradually increasing thus causing AFto reach epidemic proportions.

So far, anti-arrhythmic drug treatment for AF is characterized by twomajor findings: inefficacy and/or intolerable side effects.

The currently available and commonly used drugs to prevent or cure AFcan be divided into two groups.

The first group consist of the so-called class-I drugs, betablockers,dronedarone and sotalol.

These drugs have a rather low efficiency ranging between 20 to 40%.Initiating and continuing these drugs requires close monitoring of thepatient as these drugs in itself can easily induce life threateningarrhythmias.

The second group consists of only one drug, namely amiodarone, which isthe most potent available drug to treat AF.

Its efficiency can range up to 65%. However, the list of possible sideeffects is practically unlimited: severe thyroid problems, severe lungdisease, irreversible tinting of the skin, visual defects, possiblecarcinogenic nature, etc.

Recently a new invasive treatment modality for atrial fibrillation wasdiscovered when the Bordeaux group of Prof. Dr. Haissaguerre found thepulmonary veins, often referred to as PV's, to be the location of thetrigger for AF.

In the following years various techniques were developed to encircle thePV's as an alternative to pharmacological therapy for treating AF.

This technique is called pulmonary vein isolation, often abbreviated asPVI.

The aim was to electrically isolate the triggers in the PV's, assuringnot a single electrical connection between the PV's and the left atriumremained.

Soon enough, it was discovered that even a small gap of for example 1 mmin the line encircling the PV's could lead to electrical reconnection ofthe PV's and hence failure of the procedure with reoccurrence of AF.

Electrophysiology, the art of treating cardiac arrhythmias, ischaracterized by the use of high-tech equipment to perform diagnosticand therapeutic interventions inside the heart.

Nowadays it is possible to successfully treat virtually every arrhythmiaby means of a percutaneous intervention. Nevertheless, curing a patientfrom AF in a safe and effective manner remains a big hurdle inelectrophysiology.

There are two types of procedures by which a PVI can be achieved.

The first group consists of technologies and devices built to encirclethe PV's point by point, making sure a continuous line is formed withoutany gaps.

In most cases a combination is used of a non-fluoroscopic technique tovisualize the left atrium with its PV's and a catheter capable ofdelivering radiofrequency (RF) or cryo-energy.

However, with this first group of procedures, it is not alwaysguaranteed that a continuous line is formed with any gaps. This canoccur because the pressure with which an ablating tip is pressed againstthe wall, the amount of energy transferred from the ablating tip to thewall, the size of the ablation spot on the vessel wall, etc. is notcompletely under control. In some cases, a gap of the order of 1 mm mayalready be too wide to ensure a successful outcome of the PVI procedure.In these cases, a repetition of the whole procedure with theaccompanying danger, discomfort, cost, etc. for the patient, is usuallydeemed necessary.

The other group consists of devices created to perform PVI in ‘onesingle shot’ consecutively in each of the four PV's.

A whole assortment of catheters or sheaths has been conceived: ballooncatheters delivering cryo-energy, laser energy, high intensity focusedultrasound, thermal energy, circular catheters delivering pulsed wave RFenergy, basket-like catheters delivering RF energy, etc.

PVI has grown from an experimental therapy to a state-of-the-artintervention that can possibly cure AF.

Acute success rates in paroxysmal AF can reach 90% in the most optimalcircumstances, with a complication rate around 6%. The most commoncomplication of PVI is cardiac tamponade due to perforation of the leftatrium by the ablation catheter.

Usually this can be dealt with by performing a percutaneous puncture ofthe pericardium with evacuation of the blood, if this proves to beinadequate, a surgical intervention by means of thoracotomy is needed.

The most feared and usually lethal complication is development of afistula between the oesophagus and the left atrium.

In the past 10 years, catheter ablation techniques in patients with AFhave evolved from an initial approach focused on the PV's and theirjunctions with the left atrium, further often abbreviated as LA, to amore extensive intervention, mainly, but not exclusively, on the LAmyocardium and its neuro-vegetative innervation.

It is now recognized that the cornerstone of most catheter and surgicalablation approaches is to isolate the PV's electrically from the LA.

Despite more or less substantial differences among the various cathetertechniques that are currently utilized worldwide, results seem to beuniformly similar, with success rates in the range from 50% to 90%depending on the patients and their type of AF (permanent, long-standingpersistent, short-standing persistent, or paroxysmal AF).

Frequently a second AF ablation procedure is necessary to improveprocedural outcome.

Procedural time to perform a PVI has evolved a great deal in the pastyears. Initially, point by point PVI regularly could take more than 6hours.

New imaging techniques shortened these laborious procedures to aboutfour to six hours.

The ‘single-shot’ procedures again are somewhat shorter, but still taketwo to three hours of procedural time in general.

Fluoroscopy time needed to perform these procedures has equallydecreased, but overall ranges between 20-40 minutes.

Because of major discomfort for the patient and the need for the patientto remain motionless during the whole procedure, PVI is performed undergeneral anesthesia in many centers around the world.

The other centers use ‘conscious sedation’ which means the patient issedated with several different drugs but without the intention tointubate and ventilate the patient.

The need to sedate the patient can cause different harmful side effects.

First of all, general anesthesia always carries a certain mortality riskfor the patient. Good ‘conscious sedation’ on the other hand is hard toaccomplish.

Under-dosing the drugs leads to patient discomfort and unsolicitedpatient movement.

Over-dosing the drugs can necessitate switching to general anesthesiaduring the procedure, which is far from obvious and can even bedangerous in many cases.

The present invention has the intention to conceive a technique which ismore acceptable for the patient, less time-consuming, safer and at leastequally efficacious in performing PVI.

U.S. Pat. No. 6,632,223 discloses a system for treating atrialfibrillation comprising a stent and a catheter able to deliver the stentnear the treatment site. The stent is self-expanding and, oncedelivered, expands to lodge against the interior wall of the pulmonaryvein. The stent can be heated by sending a current through electricalwires in the catheter which are connected to the stent. The thus heatedstent may ablate a circumferential blocking lesion of the PV wall. Theablation occurs while the catheter is physically connected to the stent.Therefore, after the ablation, the stent may be disconnected from thecatheter and remain in place e.g. to prevent stenosis. This patent doesnot disclose the possibility of heating the stent by externalenergy-providing means, i.e. the possibility of heating the stent whenit is not physically connected to the catheter. Also, it does notdisclose the possibility of using materials which show magnetichysteresis for at least part of the stent. Thereby, it is not easy tocontrol the ablation temperature of the stent, in fact, the energydelivered to the stent should be monitored very closely as it depends ona multitude of factors, such as the electrical resistance of the stent,the amount and type of electrical current that is sent through thewires, the resistance of these wires, the quality of the thermal contactbetween stent and vessel wall.

Us patent application 2005/0027306 discloses a catheterization devicefor delivering a self-expanding stent. The device has an inner shaft andan outer shaft moveable with respect to the inner shaft. Theself-expanding stent is received on the inner shaft adjacent its distalend. A tapered tip is located on the inner shaft distal end and it formsa smooth transition from the delivery device to a guidewire extendingtherethrough. A handle allows a practitioner to deploy the stent singlehandedly. The stent may have its segments in a first radialconfiguration for delivery of the stent or the stent may have aplurality of segments in a first radial configuration and a plurality ofsecond segments in a second radial position.

US patent application 2005/0101946 discloses another method and systemfor treating AF by ablation of a pulmonary vein, using a stent which hasa resonant circuit. The stent can be implanted at the site of ablationand subsequently activated by external energy-providing means, inparticular by an electromagnetic field with the resonating frequency ofthe resonant circuit of the stent. The application does not disclose thepossibility of using materials which show magnetic hysteresis for atleast part of the stent, and to use the hysteresis effect for activatingthe stent. Thereby, it is also in this way not easy to control theablation temperature of the stent. The energy delivered to the stentshould be monitored very closely as it depends on a multitude of factorsand the temperature of the stent is not under control, such as theelectrical resistance of the stent and the resonant circuit of thestent, the magnitude of the RF field at the site of the stent, thequality of the thermal contact between stent and vessel wall.

European patent application EP 1 036 574 discloses a device and methodfor heating an implanted stent up to a certain temperature, usingexternal energy-providing means. The stent can be heated up through theeffect of magnetic hysteresis. However, in this patent application, thetemperature is controlled by an external controlling system whichmeasures the temperature of the stent via e.g. an infrared camera, andalters the energy provided with the external energy-providing meansaccordingly. Hereby, it is not explicitly disclosed that the system isused for ablation. Furthermore, the temperature is controlled by anexternal feedback system, and not e.g. by the material properties of thestent. Moreover, European patent application EP 1 036 574 does notdisclose that the stent or implant may subtend at least a substantiallycomplete circumferential band of the vessel's inner wall.

U.S. Pat. No. 7,235,096 discloses an implantable stent for treating adamaged body lumen, which comprises tubular stent body having severalinterconnected microholes distributed throughout the body uniformallyalong the entire length of the body. The tubular stent body has severalinterconnected microholes distributed throughout the stent bodysubstantially uniformally along the entire length of the stent body; theseveral microholes are small so as to promote an organized growthpattern of infiltrating cells throughout the stent body, and the stentbody is otherwise substantially free of holes larger than themicroholes; the stent body is formed from a fibrous three dimensionalnon-woven matrix. The patent also discloses a stent system comprisingthe stent in spaced juxtaposition to an energy source fortranscutaneously applying energy to the stent, thereby causing thetemperature of the stent to increase to a temperature above bodytemperature (preferably 38-49° C.). It further discloses an active stentcomprising the stent and further comprising live cells growing in theinterconnected microholes. A method for measuring flow of a fluidthrough a body lumen is disclosed, involving: implanting the stent intoa body lumen having a flow of fluid through it; energizing the implantedstent transcutaneously to raise its temperature above body temperature;monitoring transcutaneously the output from at least one of thetemperature sensors upon cessation of the energizing to determine thecooling rate at each of the at least one sensor: and obtaining the flowrate of the fluid through the stent from the cooling rate at the atleast one sensor. Also disclosed is a method for treating a tubular bodyorgan in a subject involving: promoting the ingrowth of living cells inthe stent; and implanting the stent into the tubular organ of thesubject prior to or following promoting the ingrowth of the living cellsso as to treat the tubular organ, whereby the stent body is formed froma fibrous three dimensional non-woven matrix.

In U.S. Pat. No. 7,235,096, the temperature of the stent can becontrolled by an at least partially external control system. In thiscase, the temperature sensor or sensors transmit the measuredtemperature to said external control system, which then controls theexternal energy source. Further, in this patent, the temperature of thestent can be controlled by the use of material with a Curie temperaturewhereby the heating of the stent occurs via hysteresis heating. Herebythe temperature of the stent is limited to the Curie temperature, sincethe mechanism of hysteresis heating only works below the Curietemperature. Both temperature control mechanisms, i.e. the externalcontrol system and the use of magnetic materials, have theirshortcomings.

The mechanism comprising the external control system leads to thenecessity of a dedicated external energy source, specifically adaptedfor receiving the temperature from the temperature sensor. Furthermore,in such a system the energy source, which in most cases will be aradiofrequent field, will need to be controlled in intensity andpossibly also in frequency in order for the implant to be kept at adesired temperature.

The mechanism of hysteresis heating has a number of difficulties,especially in finding the correct alloy with an optimal Curietemperature. As this optimal temperature may be different case-by-case,a different alloy may need to be found for different temperatures.

There remains a need in the art for improved devices, systems andmethods for the ablation of a substantially complete circumferentialband around a vessel's wall from the inside. The present invention aimsto resolve at least some of the problems mentioned above, e.g. to makesure that the ablation is performed for a substantially completecircumferential band around a vessel's wall from the inside, that theablation itself can be triggered with external means and this multipletimes if necessary, that the ablation temperature is well under controland does not depend on less-controlled elements in the treatment or onan intricate monitoring system, etc.

The present invention tries to overcome the problems by providing animplant with a built-in temperature control means, whereby said controlmeans are capable of keeping the temperature of at least part of theimplant to or below a desired temperature. The present invention alsoprovides a system and method for heating an implant to or up to adesired maximal temperature.

SUMMARY OF THE INVENTION

The present invention provides a system of one or more implant devicesand excitation device, an implant device and a method using the systemand one or more devices for the treatment of arterial and venousstructures. The present invention also concerns implant devices, asystem of implant devices and external excitation means, and a methodfor positioning one or more implant devices in a vessel, andsubsequently heating these implant devices, preferably simultaneously,thereby transferring heat from implant devices to the vessel's innerwall.

In a first aspect, the present invention provides a system for ablationof at least a part of a vessel's wall from the inside, comprised of

-   -   a self-expanding implant device, adapted to be implanted and        deployed within said vessel; whereby said implant comprises an        ablation region along at least a portion of its length, said        ablation region being adapted for surface contact with said        vessel and said ablation region subtending at least a        substantially complete circumferential band and being effective        to ablate a signal-blocking path within said vessel upon        application of energy to the implant;    -   external energy-providing means, which are spatially separated        from the implant device and able to provide energy to the        implant device for increasing the temperature of the ablation        region of the implant device up to an ablation temperature.

In a preferred embodiment, the system comprises more than one implantdevice, each of which adapted to be implanted and deployed within one ormore vessels. These implant devices can each be adapted to be implantedand deployed within one or more pulmonary veins.

In a particular preferred embodiment, one or more implant devices of thesystem comprise a proximal portion having a first diameter and a distalportion having a second diameter that is less than the first diameterand that is sufficient to enable said implants to seat within one ormore vessels.

In a preferred embodiment, at least part of the one or more implantdevices of the system is made from at least one material which showsmagnetic hysteresis, such as a ferromagnetic, ferrimagnetic oranti-ferromagnetic material. Furthermore, the external energy-providingmeans may create a time-varying magnetic field at the position of theone or more implant devices. In a more preferred embodiment, thistime-varying magnetic field is created by an electric coil through whicha time-varying electrical current is sent.

In another embodiment, the system also comprises

-   -   a sheath suitable for transporting and delivering the one or        more implant devices to or near the desired position in the one        or more vessels;    -   a guidewire suitable for sequentially guiding the sheath with        the one or more implants to the desired position in the one or        more vessels.

In a second aspect, the present invention provides a self-expandingimplant device adapted to be implanted and deployed within a vessel;said implant comprising an ablation region along at least a portion ofits length, the ablation region being adapted for surface contact withthe vessel and the ablation region subtending at least a substantiallycomplete circumferential band and being effective to ablate asignal-blocking path within the vessel upon application of energy to theimplant; whereby said ablation region comprises at least one materialwhich shows magnetic hysteresis, such as a ferromagnetic, ferrimagneticor anti-ferromagnetic material.

In a similar aspect, the present invention provides a, preferablyself-expanding, implant device adapted to be implanted and deployedwithin a vessel, said implant comprising an ablation region along atleast a portion of its length, the ablation region being adapted forsurface contact with the vessel and for subtending at least asubstantially complete circumferential band or a spiraling band and saidablation region effective to ablate a signal-blocking path within thevessel upon application of energy to the implant device, wherebypreferably said ablation region comprises at least one material whichshows magnetic hysteresis, such as a ferromagnetic, ferrimagnetic oranti-ferromagnetic material.

In another similar aspect, the present invention provides an implantcomprising an electrical circuit comprising a pick-up coil, a heatercoil and a temperature-controlled switch which comprises a closedposition and an interrupted position. Said switch preferably comprises abi-metallic component and/or a thermistor, such as a PTC thermistorand/or said switch preferably comprises a temperature sensor and a,preferably digital, thermostat connected to said sensor and to saidswitch for interrupting said switch and thus said electrical circuitwhen said sensor measures a pre-determined temperature.

In a preferred embodiment, the implant device is adapted to be implantedand deployed within a pulmonary vein. In a more preferred embodiment,said ablation region of said implant device is adapted for surfacecontact with said pulmonary veins and for subtending at least asubstantially complete circumferential band for ensuring PVI.

In a particular preferred embodiment, parts of the implant device aremade from more than one material showing magnetic hysteresis and whichhave different Curie or Néel temperatures.

In a more preferred embodiment the implant device is suitable forlong-term implantation. In another preferred embodiment, the implantdevice is a bio-resorbable implant device or an implant that disappears,e.g. by evaporation, after one or more ablations. Furthermore, theimplant device may comprise a proximal portion having a first diameterand a distal portion having a second diameter that is less than thefirst diameter and that is sufficient to enable said implant device toseat within a vessel. The implant device may further comprise anchoringmeans at or near the proximal or distal portion of said implant device,said anchoring means being suitable for keeping the device at or nearthe same position compared to the vessel's inner wall.

In a preferred embodiment, part of said implant device which can comeinto contact with the patient's blood when said implant device isimplanted, is thermally isolated from the rest of the implant devicesuch that the blood is not heated or overheated during the excitation ofthe implant device. Such part can comprise an adluminal coating or alayer with high isolation characteristics.

In a preferred embodiment, said implant comprises a thermoactive coatingcomprising an activation temperature between 35° C. and 37° C. so thatthe body temperature would trigger activation. In an alternativelypreferred embodiment, said implant comprises a thermoactive coatingcomprising an activation temperature above 45° C. so that activation istriggered only when said ablation region is heated by said externalenergy-providing means.

In a preferred embodiment, the implant device comprises a core region ofmaterial with a certain Curie temperature, surrounded by other materialwith thermal and/or elastic properties suitable for the implant device'spurpose.

In an embodiment, said implant comprises substances capable of producinga lesion of limited necrosis and/or neurotoxicity.

In a preferred embodiment, the implant device comprises cavities whichare filled with one or more substances and which open when the implantis heated. In a more preferred embodiment, these substances are mixedbefore being released into the patient's body or vessel wall, e.g. todeliver a two-component neurotixine. In another preferred embodiment,these substances are a selection or a composition of one or more of thefollowing substances:

-   -   ethanol;    -   tetrodotoxin and batrachotoxin;    -   maurotoxin, agitoxin, charybdotoxin, margatoxin, slotoxin,        scyllatoxin or hefutoxin;    -   calciseptine, taicatoxin, calcicludine, or PhTx3;    -   botulinum toxide;    -   cytochalasin D, rapamycin, sirolimus, zotarolimus, everolimus,        paclitaxel;    -   glutamate;    -   isoquinoline;    -   N-methyl-(R)-salsolinol;    -   Beta-carboline derivates.

In a further aspect, the present invention provides a system comprisingone, two, three, four or more implant devices, such as 5, 6, 7, 8, 9 or10 or more implant devices according to the present invention.Preferably this system comprises external energy-providing means, whichare spatially separated from said implant devices and able to provideenergy to said implant devices for increasing the temperature of theablation regions of the implant devices up to an ablation temperature,and/or a sheath suitable for transporting and delivering the one or moreimplant devices to or near the desired position in the one or morevessels, and/or a guidewire suitable for sequentially guiding the sheathwith the one or more implants to the desired position in the one or morevessels. In a preferred embodiment, the system comprises one, two, threeor four implant devices according to the present invention, each ofwhich adapted for a corresponding pulmonary vein.

In yet a further aspect, the present invention provides a method for thetreatment of a patient with atrial fibrillation by pulmonary veinisolation via ablation of a substantially complete circumferential bandon one or more pulmonary veins' walls from the inside, comprising thesteps of

-   -   implanting one or more implant devices in one or more pulmonary        veins by means of a sheath and a guidewire, said implant devices        each comprising an ablation region along at least a portion of        their length, said ablation regions being adapted for surface        contact with said pulmonary veins and said ablation regions        subtending at least a substantially complete circumferential        band and being effective to ablate a signal-blocking path within        said pulmonary veins upon application of energy to said implant        devices;    -   retracting the sheath and guidewire;    -   subsequently heating the ablation region of the one or more        implant devices by external energy-providing means, which are        spatially separated from the implant device.

In a similar aspect, the present invention provides a method for heatingone, two or more implant devices, which are suitable to be implanted inone, two or more vessels, comprising the steps of:

-   -   subsequently positioning said implant devices in said vessels by        means of a sheath and a guidewire, said implant devices each        comprising an ablation region along at least a portion of their        length, said ablation region subtending at least a substantially        complete circumferential band or a substantially spiraling band,        said implant devices effective for ablating a signal-blocking        path within said vessels upon application of energy to said        implant devices;    -   retracting the sheath and guidewire;    -   heating the ablation region of said implant devices by external        energy-providing means which are spatially separated from said        implant devices characterized in that said heating occurs after        said sheath and guidewire are retracted and said heating of said        implant devices occurs simultaneously.

In a preferred embodiment of the method, a recovery period is observedprior to heating the ablation region of the one or more implant devicesby external energy-providing means. Furthermore, this recovery periodmay be long enough to allow the one or more implant devices to beintegrated into the vessel wall or endothelialized.

In a particular preferred embodiment of the method, the step of heatingthe ablation region of the one or more implant devices by externalenergy-providing means, which are spatially separated from the implantdevice, is performed more than once, e.g. at well-spaced time-intervals,whenever it is deemed necessary, etc.

In a more preferred embodiment of the method, one or more implantdevices as described in this document are being used.

In a still more preferred embodiment of the method, use is made of asystem as described in this document.

DESCRIPTION OF FIGURES

FIGS. 1 to 5, and 9 to 11 schematically represent different embodimentsof an implant for the treatment of arterial and venous structuresaccording to the invention.

FIGS. 6 to 8 schematically represent a detail of a portion of an implantaccording to the invention.

FIG. 12 schematically represents an embodiment of a sheath withguidewire and implant device.

FIG. 13 schematically shows the way the catheterization can be done inorder to deliver one or more implants in the PVs.

FIG. 14 schematically represents an embodiment of the externalenergy-providing means as it can be used for treating a patient.

FIG. 15 schematically represents an embodiment of an implant in place ata PV.

FIG. 16 shows a magnetic hysteresis loop for a ferromagnet: H is theintensity of the magnetic field, M is the magnetic moment of the sample,H_(e) is the coercive field, M_(r) is the residual magnetic moment, andM_(s) is the saturation magnetic moment. The nonlimiting hysteresis loopis shown by the dotted line. The domain structure of the sample forcertain points on the loop is shown schematically.

FIG. 17 shows the typical temperature dependence of the hysteresis loopof a magnetic material with Curie or Néel temperature of 140° C.

FIG. 18 shows an embodiment of an implant which has an hour-glass shape,whereby near the middle region, where the diameter becomes smaller, aset of heating rings is attached around the hour-glass shaped part ofthe implant.

FIG. 19 shows an embodiment of an implant comprising a fuse, so that atcertain temperatures, the circuit that may be generated getsinterrupted. FIG. 19 a shows a detailed view of the fuse.

In a different configuration, as shown in FIG. 20, the metal implant canbe build up of memory shape alloys. Details of the on and off positionof the switch or fuse are shown in FIGS. 20 a and 20 b respectively.

In a still different configuration as shown in FIG. 21 and a detail inFIG. 21 a, the implant consists of two different materials.

An embodiment of the implant with an extensive coating formed around theimplant, but almost exclusively on the ADLUMINAL side is illustrated inFIG. 22.

FIG. 23 illustrates the concept of the present invention whereby animplant device is provided with a built-in thermal switch.

FIG. 24 illustrates the dimensions of an implant in an expanded positionin a vessel.

FIGS. 25 a-g illustrate different embodiments of the present invention,whereby the shape and absolute and relevant sizes of the coils maydiffer between different embodiments.

FIG. 26 illustrates that the heat is deposited mainly near the winding,but that it is possible that also the outer side of the vessel can beheated to an increased temperature.

Further embodiments comprising e.g. a PTC or thermistor switch, areillustrated in FIGS. 27 a-b for essentially cylindrical implants.

An AC-DC converter may be part of a larger electronic circuit which canbe attached to a pcb and coupled to the coils as illustrated in FIG. 28.

FIGS. 29 a-d illustrate electronic circuits which can be used inembodiments of the implant of the present invention.

FIGS. 30 a-34 illustrate embodiments of external energy providing meanswhich can be used in a system or method of the present invention forproviding energy to the implant by providing a time-varying magneticfield at the position of the implant.

DETAILED DESCRIPTION OF THE INVENTION

The present invention concerns a system of one or more implant devicesand excitation device, an implant device and a method using the systemand one or more devices for the treatment of arterial and venousstructures. The present invention also concerns implant devices, asystem of implant devices and external excitation means, and a methodfor positioning one or more implant devices in a vessel, andsubsequently heating these implant devices, preferably simultaneously,thereby transferring heat from implant devices to the vessel's innerwall.

Unless otherwise defined, all terms used in disclosing the invention,including technical and scientific terms, have the meaning as commonlyunderstood by one of ordinary skill in the art to which this inventionbelongs. By means of further guidance, term definitions are included tobetter appreciate the teaching of the present invention.

As used herein, the following terms have the following meanings:

“A”, “an”, and “the” as used herein refers to both singular and pluralreferents unless the context clearly dictates otherwise. By way ofexample, “a compartment” refers to one or more than one compartment.

“About” as used herein referring to a measurable value such as aparameter, an amount, a temporal duration, and the like, is meant toencompass variations of +/−20% or less, preferably +/−10% or less, morepreferably +/−5% or less, even more preferably +/−1% or less, and stillmore preferably +/−0.1% or less of and from the specified value, in sofar such variations are appropriate to perform in the disclosedinvention. However, it is to be understood that the value to which themodifier “about” refers is itself also specifically disclosed.

“Comprise,” “comprising,” and “comprises” and “comprised of” as usedherein are synonymous with “include”, “including”, “includes” or“contain”, “containing”, “contains” and are inclusive or open-endedterms that specifies the presence of what follows e.g. component and donot exclude or preclude the presence of additional, non-recitedcomponents, features, element, members, steps, known in the art ordisclosed therein.

The recitation of numerical ranges by endpoints includes all numbers andfractions subsumed within that range, as well as the recited endpoints.

The expression “% by weight” (weight percent), here and throughout thedescription unless otherwise defined, refers to the relative weight ofthe respective component based on the overall weight of the formulation.

The expressions “implant” and “implant device” are used interchangeablyin this application. An implant device as used in the present context,refers to an artificial tube or tube-like device, i.e. a device whichhas a circumferential wall and which is at least partly open at the topand at the bottom, whereby said circumferential wall may or may not haveopenings or holes, said tube or tube-like device intended to be placedinside a vessel of the body of a patient, e.g. a vein, or inside avessel of a human or animal corpse or model of a human or animal body.In the present context, the terms “implant” and “implant device” do notnecessarily mean that the device is placed inside a vessel to keep thisvessel open for fluids, although this can be one of the effects of thedevice. The implant device is, however, meant to be seated in a fixedposition compared to the vessel and not to move due to fluid flowthrough the vessel. When using the term “implanted” device, it is meantthat the implant or implant device has been implanted. In an embodiment,the implant device is a stent device, meaning that the device has theintended effect of keeping the vessel open for fluids when implanted.

The terms “catheter” and “sheath” are used interchangeably in thisapplication.

The term “guidewire” is used in this application for a device which canbe controllably guided when inserted into a body. In a preferredembodiment, it is a catheter, i.e. a guiding catheter. In anotherembodiment, it is solid and does not have a lumen.

The terms “Curie temperature” and “Néel temperature” refer to thetemperature above which ferromagnetic, anti-ferromagnetic andferrimagnetic materials become para- or diamagnetic, and are usedinterchangeably in the following.

“Resistive heating” and “Joule heating” here and throughout this textare used as synonyms and refer to the process by which the passage of anelectric current through a conductor releases heat.

“Thermal switch” and “temperature-controlled switch” here and throughoutthis text are used as synonyms and refer to a switch capable of closingor opening one or more electrical circuits, depending on the value of atemperature. This temperature may be the temperature at the position ofthe switch, or may be the temperature as obtained on a differentposition. Specific embodiments of thermal switches are presented furtherin this text.

In a first aspect, the present invention provides a system for ablationof at least a part of a vessel's wall from the inside, comprised of

-   -   a self-expanding implant device, adapted to be implanted and        deployed within said vessel; whereby said implant comprises an        ablation region along at least a portion of its length, said        ablation region being adapted for surface contact with said        vessel and said ablation region subtending at least a        substantially complete circumferential band and being effective        to ablate a signal-blocking path within said vessel upon        application of energy to the implant;    -   external energy-providing means, which are spatially separated        from the implant device and able to provide energy to the        implant device for increasing the temperature of the ablation        region of the implant device up to an ablation temperature.

The implant device is self-expanding, for example, being formed of ashape memory alloy, and is configured to lodge against the interior wallof e.g. a pulmonary vein. The implant may be formed as a loop, helix,progressively wound helix or other suitable shape. It may have anchoringmeans such as hooks or barbs near the ends, preferably near the proximalend at the side of the antrum or near the distal end at the side of theostium or deeper into the vessel when implanted in a PV near the leftatrium. The implant device may comprise an ablation region which is incontact with the ablation region of the vessel's wall. Preferably, theablation region comprises a substantially complete circumferential bandaround the vessel's wall. The ablation region may comprise a completecircumferential band around the vessel's inner wall, or the ablationregion may comprise a complete circumferential band around the vessel'swall and this for the complete thickness of the wall. With‘substantially’ is meant that the ablation region is such that allelectric signals arising at one side of the ablation region do not reachthe other side, i.e. a signal-blocking path is ablated. Energy can beprovided to the implant device by external means through electromagneticradiation, through hysteresis heating via a time-varying magnetic field,by direct and indirect induction and by Joule heating, by acoustic,mechanical-vibrational and chemical energy means, by a thermal/chemicalor mechanical/chemical release system.

One of the advantages of the present invention over prior arttechniques, is that the one or more implant devices can be heated upsimultaneously, i.e. the delivery of energy to the implants happens atthe same time and does not need to be done sequentially. This saves timeand increases the patient's comfort. Through built-in control of thetemperature, e.g. by using magnetic material with a specified Curietemperature or by using the proper insulation material in the implant,additional energy delivery will not further increase the temperaturebuilt-up in the implant.

By ‘external’ energy-providing means is meant that these means arespatially separated from the implant device, i.e. there is no physicalconnection between the energy-providing means and the implant device,or, more specifically, the energy-providing means are completely outsidethe patient's body and the patient's skin can remain intact while theenergy is provided.

The temperature of ablation region is specified according to the needsof the treatment. Depending on the ablation temperature needed, theimplant device can be engineered to be warmer at certain regions than inother regions by using the magnetic and thermal properties of thematerials of which the implant device is composed. In an embodiment,parts of the implant device may be thermally isolated from other partsof the implant device or from parts of the body or bodily fluids.

In a preferred embodiment, the system comprises more than one implantdevice, each of which adapted to be implanted and deployed within one ormore vessels. These implant devices can each be adapted to be implantedand deployed within one or more pulmonary veins.

In about 60% of the patients, four PVs debouch separately into the leftatrium. However, in other patients, two PVs have a common debouch and instill other patients, there can be a fifth vein debouching in the leftatrium. It should be clear that the one or more implant devices can beadapted to fit into all these veins, also for the less occurring cases.

In a particular preferred embodiment, one or more implant devices of thesystem comprise a proximal portion having a first diameter and a distalportion having a second diameter that is less than the first diameterand that is sufficient to enable said implants to seat within one ormore vessels.

Mainly for the right PVs, an implant as described above can be used,since these PVs usually have a different diameter in their ostium thanin their antrum.

In a particular preferred embodiment, one or more implant devices of thesystem comprise a proximal portion having a first diameter and a distalportion having a second diameter that is greater than or equal to thefirst diameter and that is sufficient to enable said implants to seatwithin one or more vessels.

Mainly for the left PVs, an implant as described above can be used,since these PVs usually have the same or a similar diameter in theirostium as in their antrum. In some cases the diameter in the distal partof the PV is larger than the diameter of the proximal part.

Obviously, the way a PV is connected to the left atrium depends on thepatient. The shape of antrum and ostium can be different for each PV andeach patient. However, it should be clear to the person skilled in theart that the proximal portion with the larger diameter is to be placednear the antrum, while the distal portion with the smaller diameter isplace near the ostium or deeper inside the PV. In case the implantdevice is implanted in another type of vessel, it should be clear thatthe shape of the implant device can be adapted so as to fit into thespecific vessel.

In order to make the shape and dimensions of the implants, it ispossible by a scanning technique such as CT-scan or MRI, to collect dataon the varying diameter of the vessel when going from the ostium to theantrum. From these data, one can derive the necessary shape anddimensions of the implants e.g. for all four PVs of a patient. Againthis measuring can be done without a surgical procedure, therebyincreasing the patient's comfort and wellbeing and reducing medicalrisks. After this measuring, the implants can be custom-made to fit thepatient's vessel or vessels.

In a preferred embodiment, at least part of the one or more implantdevices of the system is made from at least one material which showsmagnetic hysteresis, such as a ferromagnetic, ferrimagnetic oranti-ferromagnetic material. Furthermore, the external energy-providingmeans may create a time-varying magnetic field at the position of theone or more implant devices. In a more preferred embodiment, thistime-varying magnetic field is created by an electric coil through whicha time-varying electrical current is sent.

Magnetic hysteresis arises in a plethora of materials. Most known andmost used are the ferromagnetic, anti-ferromagnetic and ferrimagneticmaterials. These have highly non-linear magnetic properties, i.e. themagnetic induction field is not directly proportional to the appliedmagnetic field inside the material. However, all these material losetheir specific magnetic properties above a certain temperature, calledthe Curie or Néel temperature. This temperature is material-specific.Above this temperature, the ferromagnetic, anti-ferromagnetic andferrimagnetic materials become para- or diamagnetic and thereby losetheir non-linear magnetic properties. The non-linear magnetic propertiesof ferromagnetic, anti-ferromagnetic and ferrimagnetic materials can bededuced from the hysteresis that is observed when applying atime-varying magnetic field.

Magnetic hysteresis is observed in magnetic materials, such asferromagnets. The main feature of ferromagnets is the presence ofspontaneous magnetization. A ferromagnet usually is not uniformlymagnetized but is divided into domains—regions of uniform spontaneousmagnetization whose degree of magnetization (the magnetic moment perunit volume) is identical, although the directions are different. Underthe effect of an external magnetic field the number and size of thedomains magnetized along the field increase at the expense of otherdomains. Moreover, the magnetic moments of certain domains may rotate inthe direction of the field. As a result the magnetic moment of thesample increases.

The dependence of the magnetic moment M of a ferromagnetic sample on theintensity H of the external magnetic field (the magnetization curve) isshown in FIG. 16. In a sufficiently strong magnetic field the sample ismagnetized to saturation (as the field increases further, the value of Mremains virtually unchanged—point A). Here the sample consists of onedomain with a magnetic moment of saturation M_(s) oriented along thefield. As the intensity H of the external magnetic field is reduced, themagnetic moment M of the sample will decline along curve I primarilybecause of the appearance and growth of domains whose magnetic moment isoriented against the field. The growth of the domains is due to themovement of the domain walls. This movement is hindered by the presencein the sample of various defects (such as impurities or inhomogeneities)that strengthen the domain walls at some points; very strong magneticfields are required to displace them. Therefore as the field H drops tozero, the so-called residual magnetic moment M_(r) (point B) isretained. A sample can be completely demagnetized only in a sufficientlystrong field of opposite direction, which is called a coercive field(coercive force) H_(c) (point C). As the magnetic field of reverseorientation is further increased, the sample is once again magnetizedalong the field to saturation (point D). Magnetic reversal (from point Dto point A) takes place along curve II. Thus, as the field undergoes acyclical change, the curve characterizing the change in the magneticmoment of the sample forms a magnetic hysteresis loop. If the field Hchanges cyclically with such limits that magnetization does not reachsaturation, a nonlimiting magnetic hysteresis loop is produced (curveIII). By reducing the extent of the change in field H to zero, thesample can be completely demagnetized (point O can be reached). Themagnetization of the sample from point O proceeds along curve IV.

In magnetic hysteresis different values of the magnetic moment Mcorrespond to the same value of the external magnetic field intensity H.This nonuniqueness is due to the influence of the states of the samplethat precede the given state (that is, to the magnetic prehistory of thesample).

The shape and size of magnetic hysteresis loops and the quantity H_(c)may range within wide limits in various ferromagnets. For example, inpure iron, H_(c)=1 oersted, and in a magnico alloy H_(c)=580 oersteds. Amagnetic hysteresis loop is strongly affected by processing of thematerial, during which the number of defects is changed. The area of amagnetic hysteresis loop is equal to the energy lost in the sample inone cycle of field change. This energy is also proportional to the totalvolume of ferromagnetic material in the sample. This energy ultimatelyis used to heat the sample. Such energy losses are called hysteresislosses. In cases when losses to hysteresis are undesirable (for example,in transformer cores and in the stators and rotors of electricalmachinery), magnetically soft materials with a low H_(c) and a smallhysteresis loop area are used. On the other hand, magnetically hardmaterials with a high H_(c) are required to manufacture permanentmagnets.

As the frequency of the alternating magnetic field (the number ofmagnetic reversal cycles per unit time) increases, other losses causedby eddy currents and magnetic viscosity are added to hysteresis losses.At high frequencies the area of the hysteresis loop increasescorrespondingly. Such a loop is sometimes called a dynamic loop, incontrast to the static loop described above.

Many other properties of a ferromagnet, such as electrical resistanceand mechanical deformation, depend on the magnetic moment. A change inmagnetic moment also brings about a change in these properties—forexample, galvanomagnetic and magnetostrictive hysteresis, respectively,are observed.

The hysteresis loop depends on the temperature. FIG. 17 shows thetypical temperature dependence of the hysteresis loop of a magneticmaterial with Curie or Néel temperature of 140° C. Note that only thetemperature dependence of the shape is characteristic and no units aregiven on the axes, the figure is meant for illustration purposes. It isobserved that the hysteresis loop changes with temperature, becomingsharper and thinner, and eventually disappearing at the Curie or Néeltemperature. From this temperature onwards, the material becomes para-or diamagnetic and no heating losses due to hysteresis are observed.This means that the material does not heat up anymore, at least not dueto hysteresis effects, and remains at the Curie or Néel temperature. (Inthe following, the two terms ‘Curie’ and ‘Néel’ temperature can be usedinterchangeably.) It should be remarked that heating due to othereffects, such as direct or indirect induction may still be possible, butthese effects are negligible in the present case, especially whencompared to the gigantic heating capabilities by hysteresis effects.

It should be now clear to the skilled person that when the ablationregion of an implant device comprises material with Curie temperature ofe.g. 40° C., the implant will be heated up to this temperature and notmore when being subjected to a time-varying magnetic field, e.g. by theexternal energy-providing means of the system of the present invention.If the ablation temperature needs to be 42° C. or 45° C., the magneticmaterial used in the implant may be altered to have this temperature asCurie temperature. This can be done by e.g. changing the composition ofan alloy of magnetic material. The Curie temperature of a magneticmaterial can be very precisely engineered.

In a preferred embodiment, the magnetic materials used in the implantdevice are a combination or alloy of the following materials: MnAs, Gd,Gd with a thin Fe overlayer, Ni—Fe alloy with around 29.5 at. % Ni whichis cooled slowly from 1000° C., Ni—Fe with 30 at. % Ni, Cr, CoO,ZnFe₂O₄, are any magnetic material with Curie or Néel temperature above10, 20, 25, 30, 35, 40° C. and/or below 75, 70, 65, 60, 55, 50, 45, 40°C.

The Curie or Néel temperatures of alloys or composite materials candepend highly on the procedure for making these materials. Especiallyannealing procedures may be important. Also other ways of altering theCurie temperatures such as ion radiation can be used to provide thedesired material. One can use any magnetic material, alloy, binaryalloy, ternary alloy or quaternary alloy with the desired Curie or Néeltemperature as specified in standard reference works such as theLandolt-Börnstein database.

In another embodiment, the system also comprises

-   -   a sheath suitable for transporting and delivering the one or        more implant devices to or near the desired position in the one        or more vessels;    -   a guidewire suitable for sequentially guiding the sheath with        the one or more implants to the desired position in the one or        more vessels.

The sheath in this embodiment includes an implant delivery systemcapable of delivering the one or more implant devices as described inthis text. An embodiment of such sheath with delivery device andguidewire is shown in FIG. 12.

In a second aspect, the present invention provides a self-expandingimplant device adapted to be implanted and deployed within a vessel;said implant comprising an ablation region along at least a portion ofits length, the ablation region being adapted for surface contact withthe vessel and the ablation region subtending at least a substantiallycomplete circumferential band and being effective to ablate asignal-blocking path within the vessel upon application of energy to theimplant; whereby said ablation region comprises at least one materialwhich shows magnetic hysteresis, such as a ferromagnetic, ferrimagneticor anti-ferromagnetic material.

Preferably said material comprises a ferrous fluid, i.e. ferromagnetic,ferrimagnetic and/or anti-ferromagnetic particles suspended in a heatconducting fluidum, whereby said material is preferably contained withinsaid implant device. In a more preferred embodiment, said implant devicecomprises one or more fluid-tight cavities comprising saidferromagnetic, ferrimagnetic and/or anti-ferromagnetic particles in saidheat conducting fluidum. In an even more preferred embodiment, saidparticles comprise any or any combination of the following materials:SrFe₁₂O₁₉, Me_(a)-2W, Me_(a)-2Y, and Me_(a)-2Z, wherein 2W isBaO:2Me_(a)O:8Fe₂O₃, 2Y is 2 (BaO:Me_(a)O:3Fe₂O₃), and 2Z is 3BaO:2Me_(a)O:12Fe₂O₃, and wherein Me_(a) is a divalent cation, wherebythe divalent cation is preferably selected from Mg, Co, Mn and Zn,and/or 1Me_(b)O:1Fe₂O₃, where Me_(b)O is a transition metal oxideselected from Ni, Co, Mn, and Zn, and/or metal alloys such asLa_(0.8)Sr_(0.2)MnO₃, Y₃Fe_(5-x)M_(x)O₁₂ where M is Al, or Gd and 0<x<2,and/or metal alloys of any combination of Pd, Co, Ni, Fe, Cu, Al, and Siand/or metal alloys of any combination of Gd, Th, Dy, Ho, Er, and Tmwith any combination of Ni, Co, and Fe and/or metal alloys RMn₂X where Ris a rare earth, such as La, Ce, Pr, or Nb and X is either Ge or Si.Particularly preferred is any or any combination of the followingalloys: NiCu with 28% or 29.6% Ni, NiPd, PdCo with 6.15% Pd, NiSi with4% Ni, (Ni,ZnO)Fe₂O₃, La_(0.8)Sr_(0.2)MnO_(x), Y₃Fe_(5-x)Al_(x)O12 with1.0×1.7. The particles can be of any size, preferably longer than 10nanometers, more preferably longer than 20 nanometers in the longestdimension, and smaller than 500 micrometers, preferably smaller than 100micrometers in the longest dimension. In certain embodiments, saidparticles are smaller than 1 micrometer, preferably smaller than 200nanometers in the longest dimension. In other embodiments, saidparticles are longer than 1 micrometer, preferably longer than 20micrometer in the longest dimension. Preferably said fluidum in whichsaid particles are suspended comprises optimal heat conductionproperties. In a preferred embodiment, said fluidum comprises a largeheat capacity. In another preferred embodiment, said fluidum comprises alow heat capacity. The exact nature, amount and combination of whichmagnetic materials to use for the particles and which fluidum to use,depends on the desired temperature and heat for e.g. inducing completecircumferential ablation of the inner wall of a pulmonary vein. In apreferred embodiment, said magnetic materials comprise a Curie or Néeltemperature of 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50,51, 52, 53, 54, 55° C. or any value in between or any combinationthereof, preferably said Curie or Néel temperature is smaller than 75°C., more preferably smaller than 70° C., even more preferably smallerthan 65° C., yet more preferably smaller than 62° C., still morepreferably smaller than 59° C., yet even more preferably smaller than57° C., still even more preferably smaller than 55° C.

In a preferred embodiment, the implant device is adapted to be implantedand deployed within a pulmonary vein.

In a particular preferred embodiment, parts of the implant device aremade from more than one material showing magnetic hysteresis and whichhave different Curie or Néel temperatures.

Different temperatures cause different lesions on different placesdepending on which ablation regions of the implant device compriseswhich material. By thermally isolating parts of the implant device whichconsist of material with different Curie temperatures, a gradation inablation temperature along the implant device is possible. Also, partscomprising material with higher heat capacities will heat up moreslowly, but will remain hot longer afterwards, etc. Engineering ofablation characteristics can be done by engineering the implant makinguse of the magnetic and thermal properties of the materials used in theimplant.

In a more preferred embodiment the implant device is suitable forlong-term implantation. In another embodiment, the implant device is abio-resorbable implant device or an implant that disappears, e.g. byevaporation, after one or more ablation procedures. In a preferredembodiment, the implant device may comprise a proximal portion having afirst diameter and a distal portion having a second diameter that isless than the first diameter and that is sufficient to enable saidimplant device to seat within a vessel. The implant device may furthercomprise anchoring means at or near the proximal or distal portion ofsaid implant device, said anchoring means being suitable for keeping thedevice at or near the same position compared to the vessel's inner wall.The anchoring means may comprise hooks or barbs or anything else knownin the art for keeping an implant device at the desired position.

In a preferred embodiment, the implant device comprises an elasticallycompressible body comprising externally triggerable portions andprovided of anchoring means. The body may be mainly made of wires andmay, in expanded or released position, be provided of a narrowingtubular shape and/or a somewhat flattened narrowing tubular shape, i.e.that the cross sections at most positions along the longitudinal axisare oval shaped or the like, suitable to be placed inside the antrum ofa pulmonary vein. The body may also comprise between two and fivecircular wires, a first bigger circular or oval wire, and furthercircular or oval wires with decreasing diameter, positioned andmaintained at a distance from each other, at least when the body is in areleased or not compressed position. The body may be built up out ofbraided metal wires (that have multiple interconnections, crossingsand/or layers which allows for numerous connections with the vascularwall in the heart, more specifically in the atria, more specifically inthe left and right atrium, more specifically in the antrum or ostium ofthe pulmonary veins. The body may be conceived as a spirally shaped wireof which the diameter gradually goes down along its longitudinal axis.The windings of the implant device may be mutually connected withbridging upstanding wire portions providing closed loops to ensure fulland circular coverage of for example the antrum/ostium of the pulmonaryveins once the device is released. The body may show longitudinal metalbeads that are outward bending, and that still show severalinterconnections between them, to ultimately form a metal cage. Theimplant device may be characterized in that the greatest distancebetween two points that can be measured on the circular or oval wires ofthe body will range from 3 to 30 mm, more specifically from 5 mm to 20mm, even more specifically from 9 mm to 13 mm, if to be implanted at theostia of the pulmonary vein. The implant device may be characterized inthat the greatest distance between two points that can be measured onthe circular or oval wires of the body of the implant device will rangefrom 5 to 50 mm, more specifically from 8 mm to 40 mm, even morespecifically from 10 mm to 30 mm, if to be implanted at the site of theantrum. The body of the implant device may be mainly made of one or moremetal alloys. The body of the implant device may comprise portions whichare externally triggerable by means of an energy field or a combinationof energy fields chosen from electromagnetic radiation, direct orindirect induction, acoustic energy, mechanical vibration, heatingand/or changing other characteristics of the implant or portionsthereof. Some of the material used in the implant device may be of thetype that reacts, for example heats, in response to a remote appliedalternating magnetic field. Energy can be provided to the implant deviceby external means through electromagnetic radiation, through hysteresisheating via a time-varying magnetic field, by direct and indirectinduction and by Joule heating, by acoustic, mechanical-vibrational andchemical energy means, by a thermal/chemical or mechanical/chemicalrelease system. The body may comprise portions made of different metalalloys with optionally different ferromagnetic properties and/orabsorption coefficients, with specific response to alternating magneticfields. Portions of the body of the implant device may be provided ofone or more coatings with varying properties. The wire or wires or otherportions of the body of the implant device is/are composed of differentlayers made of different alloys and/or of other materials. The implantdevice may be further characterized in that different coatings or layersrepresent different responses to externally applied energy fields, forexample to externally applied alternating magnetic fields. An adluminalcoating or layer with high isolation characteristics may be provided tothe implant device. The body of the implant device may haveself-expanding properties thanks to the elastic characteristics of thematerial used, and thanks to the geometry of the body, and furtherexpansion is stopped when it encounters a counter pressure of about 10to 40, preferably 20 to 30, more preferably 22 to 28, even morepreferably around 25 mm Hg, equal to the distension pressure needed toalter the left atrium's anatomy. The implant device may be characterizedin that it is provided of toxic substances that are only released uponintroduction into the pulmonary vein/antrum, for example after applyingan external energy field, which toxic substances then produce a lesionof limited necrosis/neurotoxicity. These toxins may include, but are notlimited to ethanol, tetrodotoxin and batrachotoxin, maurotoxin,agitoxin, charybdotoxin, margatoxin, slotoxin, scyllatoxin andhefutoxin, calciseptine, taicatoxin, calcicludine, and PhTx3, botulinumtoxine, cytochalasin D, rapamycin, sirolimus, zotarolimus, everolimus,paclitaxel, glutamate, isoquinoline, N-methyl-(R)-salsolinol,Beta-carboline derivates. The implant device may be provided of micropores wherein substances are provided, which can be released by atriggering energy field. The implant device may be provided of athermoactive coating which is only activated upon temperatures above 35°C. so that the body temperature would trigger activation. The implantdevice may be provided of a thermoactive coating which is only activatedupon temperatures above 45° C. so that an external application of anenergy field would trigger activation. The implant device may beprovided of anchoring means which mainly consist of the elongated shapeand/or the expanding forces optionally in combination with the wiredstructure allowing partial insertion or impression in the wall of theheart, more specifically of the atria, more specifically of the left andright atrium, more specifically of the antrum or ostium of the pulmonaryveins. These anchoring means may also comprise hooks or barbs or thelike, optionally provided on the outwardly directed portions of theimplant.

In a preferred embodiment, said implant device comprises cavities whichare filled with one or more substances and which open when the implantis heated and/or which open when the implant acquires body temperature,and/or whereby said implant comprises a coating comprising one or moresubstances.

In a preferred embodiment, an implant device according to the presentinvention comprises a maximal circumference and a minimal circumferenceand a ratio between maximal and minimal circumference, whereby saidratio is smaller than 10, preferably smaller than 9, more preferablysmaller than 8, even more preferably smaller than 7, yet more preferablysmaller than 6 and larger than 1.1, preferably larger than 1.5, morepreferably larger than 2, even more preferably larger than 2.5, yet morepreferably larger than 3. In a preferred embodiment, the implant devicecomprises a variable circumference along a longitudinal direction of theimplant, said circumference varying between at least 20 mm, preferablyat least 25 mm, more preferably at least 30 mm, even more preferably atleast 36 mm, yet more preferably at least 42 mm, still more preferablyat least 48 mm and at most 375 mm, more preferably at most 350 mm, evenmore preferably at most 325 mm, yet more preferably at most 300 mm,still even more preferably at most 275 mm, yet even more preferably atmost 250 mm. Such a ratio or dimension may be necessary to ensure thatan essentially circumferential band of the vessel's inner wall would besubtended, in particular in or near the antrum of said vessel, inparticular if the vessel is a pulmonary vein.

In a particularly preferred embodiment, said circumference may be atmost 200%, preferably at most 190%, more preferably at most 180%, evenmore preferably at most 170%, yet more preferably at most 160%, stillmore preferably at most 150% of the original diameter of the vessel forwhich the implant device is adapted, e.g. of the pulmonary vein or ofthe antrum of the pulmonary vein when the self-expanded implant deviceis in an expanded state.

In a preferred embodiment, the implant device comprises an outer surfacecomprising zig-zag or woven or braided material, drawn tubes,eccentrically drawn tubes, hollow struts, hollow struts filled withfluid, or any combination thereof.

In a preferred embodiment, an implant device according to the presentinvention comprises an essentially cylindrical shape preferablycomprising a diameter which is at least 2 mm, preferably at least 3 mm,more preferably at least 4 mm, even more preferably at least 5 mm, yetmore preferably at least 6 mm and at most 20 mm, preferably at most 16mm, more preferably at most 13 mm, even more preferably at most 10 mm,yet more preferably at most 9 mm. Such a shape or dimension may benecessary to ensure that a circumferential or spiraling band of thevessel's inner wall would be subtended, in particular in an essentiallycylindrical portion of said vessel.

In a preferred embodiment, an implant device according to the presentinvention comprises a distal portion and a proximal portion, wherebysaid ablation region is located within 50%, preferably within 40%, morepreferably within 30% of the implant's total length from the proximalportion. In a preferred embodiment, an implant device according to thepresent invention comprises a distal portion and a proximal portion,whereby said ablation region is located within 25 mm, preferably within20 mm, more preferably within 15 mm from the proximal portion. If theimplant device is positioned in a pulmonary vein for e.g. PVI, theproximal portion is intended to be positioned near the antrum, while thedistal portion is intended to be positioned towards the ostium. Locatingthe ablation region of the implant device closer to the proximal portionthus is more efficient to obtain a circumferential ablation in theantrum of the PV.

In a preferred embodiment, the implant device comprises a distal portionand a proximal portion, and comprising an anchoring device connected tothe ablation region of said implant via a thermally insulatingconnection for preventing overheating of said anchoring device,preferably whereby said anchoring device is connected to the distalportion. The anchoring device may comprise different material than therest of the implant device. In particular, the anchoring device may havedifferent thermal characteristics due to its dimensions, shape ormaterial. The anchoring device may be connected to the distal portion ofthe implant device in order to have optimal anchoring in e.g. the ostiumof a PV. The thermally insulating connection may comprise thermallyinsulating material, or its shape and dimensions may increase thermalinsulation, e.g. a number of thin straps or wires attaching theanchoring device to the ablation region.

In a preferred embodiment, the system for the treatment of arterial andvenous structures, comprises an implant device according to any of theabove embodiments and an excitation or energy-providing devicepreferably conceived to be used from the exterior of the patient, afterbeing provided of an implant device, whereby the excitation serves tochange the characteristics of the implant device in order to treat thearterial or venous structure where the implant device is located. Theexcitation device for the treatment of arterial and venous structures,may be conceived to be used in cooperation with an implant deviceaccording to any embodiment described in this text.

In a preferred embodiment the part of the implant device which can comeinto contact with the patient's blood when said implant device isimplanted, is thermally isolated from the rest of the implant devicesuch that the blood is not heated or overheated during the excitation ofthe implant device. Such part may comprise an adluminal coating or alayer with high isolation characteristics. It is clear that heating ofthe blood should be avoided as much as possible for the benefit andcomfort of a patient.

In another embodiment, the implant device comprises a core region ofmaterial with a certain Curie temperature, surrounded by other materialwith thermal and/or elastic properties suitable for the implant device'spurpose. As such, one can engineer the temperature profile through theimplant device. It should be clear that the parts of the implant whichare meant to contact the vessel wall and the form lesions by ablation,should be heated mostly while other parts of the implant, which are incontact with the vessel or the blood and are not meant to form lesions,should receive as little heat as possible for the wellbeing of apatient.

In still another embodiment, the implant device comprises cavities whichare filled with one or more substances and which open when the implantis heated. In a preferred embodiment, these substances are mixed beforebeing released into the patient's body or vessel wall, e.g. to deliver atwo-component neurotixine. In a more preferred embodiment, thesesubstances are a selection or a composition of one or more of thefollowing substances:

-   -   ethanol;    -   tetrodotoxin and batrachotoxin;    -   maurotoxin, agitoxin, charybdotoxin, margatoxin, slotoxin,        scyllatoxin or hefutoxin;    -   calciseptine, taicatoxin, calcicludine, or PhTx3;    -   botulinum toxide;    -   cytochalasin D, rapamycin, sirolimus, zotarolimus, everolimus,        paclitaxel;    -   glutamate;    -   isoquinoline;    -   N-methyl-(R)-salsolinol;    -   Beta-carboline derivates.

With such implants, it becomes possible to release the desiredsubstances into the vessel wall or the blood stream at the desiredmoment, by heating the implant with e.g. external energy providingmeans. Furthermore, the implant and cavities in the implant may bedesigned such that the two components of e.g. a two-componentneurotixine, are mixed before being released into the body.

In a preferred embodiment, an implant device according to the presentinvention comprises one or more deposits of toxin, preferably on anouter surface of said device, said deposits covered by a metal layercapable of being resolved by heating, preferably hysteresis heating.

In a similar aspect, the present invention provides an implantcomprising an electrical circuit comprising a pickup coil, a heater coiland a temperature-controlled switch which comprises a closed positionand an interrupted position.

Said switch preferably comprises a bi-metallic component and/or athermistor, such as a PTC thermistor and/or said switch preferablycomprises a temperature sensor and a, preferably digital, thermostatconnected to said sensor and to said switch for interrupting said switchand thus said electrical circuit when said sensor measures apre-determined temperature. Preferably said switch is arranged to changefrom said closed to said open position when a temperature at or nearsaid implant is higher than a pre-defined ablation temperature. In apreferred embodiment, said switch is arranged to change from said opento said closed position when a temperature at or near said implant islower than a pre-defined switching temperature. In one embodiment, saidablation temperature is equal to said switching temperature. In anotherembodiment, said switching temperature is different from said ablationtemperature, preferably said switching temperature is lower than saidablation temperature, e.g. at least 0.01° C., 0.1° C., 0.5° C., 1° C.,2° C., 3° C., 4° C., 5° C., 6° C., 7° C., 8° C., 9° C., 10° C., 11° C.,12° C., 13° C., 14° C., 15° C., 16° C., 17° C., 18° C., 19° C., 20° C.lower than said ablation temperature. In a preferred embodiment, saidcircuit comprises more than one switch, e.g. 2, 3, 4 or more switches,preferably connected in series, for redundancy, i.e. for ensuring atleast one switch functions as desired.

In yet another similar aspect, the present invention provides an implantfor treating atrial fibrillation by multiple ablation of the inner wallsof a pulmonary vein via heating, comprising an electrical circuitcomprising a pickup coil, a heater coil and a temperature-dependentLC-circuit, whereby said LC circuit comprises a resonant frequency whichis temperature-dependent.

The pickup coil of the above implants is arranged for inducing anelectrical current through an electrical circuit to which it isconnected, under the influence of a time-varying magnetic flux throughsaid pick-up coil. Thereto, said pickup coil preferably comprises a lowresistance and a high inductance.

Preferably, said pickup coil comprises a resistance which is larger than0.02 Ohm, preferably larger than 0.05 Ohm, more preferably larger than0.1 Ohm, even more preferably larger than 0.15 Ohm, yet more preferablylarger than 0.2 Ohm, still more preferably larger than 0.3 Ohm, stilleven more preferably larger than 0.5 Ohm, and/or smaller than 30 Ohm,preferably smaller than 30 Ohm, more preferably smaller than 25 Ohm,even more preferably smaller than 20 Ohm, yet more preferably smallerthan 15 Ohm, still more preferably smaller than 10 Ohm, yet even morepreferably smaller than 5 Ohm, most preferably about 1 Ohm.

Preferably, said pickup coil comprises an inductance which is largerthan 0.02 pH, preferably larger than 0.05 pH, more preferably largerthan 0.1 pH, even more preferably larger than 0.15 pH, yet morepreferably larger than 0.2 pH, still more preferably larger than 0.3 pH,still even more preferably larger than 0.5 pH, and/or smaller than 30pH, preferably smaller than 30 pH, more preferably smaller than 25 pH,even more preferably smaller than 20 pH, yet more preferably smallerthan 15 pH, still more preferably smaller than 10 pH, yet even morepreferably smaller than 7 pH, most preferably about 4 pH, e.g. 1 pH, 2pH, 3 pH, 4 pH, 5 pH, 6 pH, 7 pH, or any value therebetween.

In a preferred embodiment, said heating coil is arranged for subtendinga substantially complete circumferential ablation region in a vessel,preferably in a pulmonary vein, for obtaining a substantially completecircumferential signal-blocking lesion on the inner wall of said vessel.Preferably said heater coil comprises a high resistance and a lowinductance.

Preferably, said heater coil comprises a resistance which is larger than0.4 Ohm, preferably larger than 1 Ohm, more preferably larger than 2Ohm, even more preferably larger than 3 Ohm, yet more preferably largerthan 4 Ohm, still more preferably larger than 6 Ohm, still even morepreferably larger than 10 Ohm, and/or smaller than 150 Ohm, preferablysmaller than 100 Ohm, more preferably smaller than 80 Ohm, even morepreferably smaller than 60 Ohm, yet more preferably smaller than 50 Ohm,still more preferably smaller than 40 Ohm, yet even more preferablysmaller than 30 Ohm, most preferably about 25 Ohm.

Preferably, said heater coil comprises an inductance which is largerthan 0.02 pH, preferably larger than 0.05 pH, more preferably largerthan 0.1 pH, even more preferably larger than 0.15 pH, yet morepreferably larger than 0.2 pH, still more preferably larger than 0.3 pH,still even more preferably larger than 0.5 pH, and/or smaller than 30pH, preferably smaller than 30 pH, more preferably smaller than 25 pH,even more preferably smaller than 20 pH, yet more preferably smallerthan 15 pH, still more preferably smaller than 10 pH, yet even morepreferably smaller than 7 pH, most preferably about 4 pH, e.g. 1 pH, 2pH, 3 pH, 4 pH, 5 pH, 6 pH, 7 pH, or any value there between.

In a particular preferred embodiment, the resistance of the heater coilis larger than the resistance of the pickup coil and/or the inductanceof the pickup coil is larger than the inductance of the heater coil.

In a preferred embodiment, the current flowing through the heater coil,when the implant is activated e.g. by external energy-providing meanssuch as by an imposed time-varying magnetic field via inductance, islarger than 0.1 A, preferably larger than 0.2 A, more preferably largerthan 0.3 A, even more preferably larger than 0.4 A, yet more preferablylarger than 0.5 A, still more preferably larger than 0.6 A, yet evenmore preferably larger than 0.7 A, still even more preferably largerthan 0.8 A, and smaller than 10 A, more preferably smaller than 8 A,even more preferably smaller than 6 A, yet more preferably smaller than4 A, still more preferably smaller than 2 A, yet even more preferablysmaller than 1.5 A, still even more preferably smaller than 1 A, mostpreferably about than 0.9 A.

The pre-determined temperature in the present invention is preferably anablation temperature for the inner wall of a vessel into which theimplant is to be placed. Preferably said ablation temperature is 37, 38,39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56,57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74,75° C. or any value in between.

In a preferred embodiment, said pick-up coil, said heater coil and saidtemperature-controlled switch comprising said bi-metallic component areconnected in series, whereby said bi-metallic component is in an openposition when heated above a pre-defined temperature, therebyinterrupting said circuit and stopping the heater coil from heating up,and whereby said bi-metallic component is in a closed position when itstemperature is below said temperature, thereby closing said circuit suchthat a current, e.g. an induced current, can flow through the heatercoil.

Preferably said implant comprises a circuit supply coil capable ofpicking up an AC current via induction from an externally appliedtime-varying magnetic field, said supply coil coupled to an AC-DCconverter for providing a DC current or voltage, preferably to saidswitch or to other electronic components of said implant.

In a preferred embodiment, the implant comprises a source electricalcircuit and a heating electrical circuit, which can be separately closedand/or open, whereby said source electrical circuit is arranged forproviding a DC voltage and/or current output from an induced AC currentin said pick-up loop. Preferably said DC output is connected to saidswitch for providing said switch with energy. Preferably said heatingelectrical circuit is arranged for heating said heater coil viaresistive heating when said switch is closed, thereby allowing a heatingcurrent to flow through said heater coil.

In a preferred embodiment, said pickup coil and said heater coil areconnected in series when said switch is closed, thereby allowing anelectrical current picked up by induction by said pickup coil to flowthrough said heater coil, thereby heating said heat coil throughresistive heating.

Preferably said heating current comprising an AC current, which may beinduced in said pick-up coil and transferred to said heater coil if saidswitch is closed, and/or said AC current may be induced in said heatercoil by external energy providing means such as an external generator.Said heating current may comprise a DC current, e.g. a DC current asprovided for by a supply coil coupled to an AC-DC convertor.

In a preferred embodiment, said implant is at least partlyself-expanding. In a preferred embodiment, said implant comprises acone-like shape for implantation into the antrum of a pulmonary vein.

Preferably, said pickup coil comprises a length which is larger than 10mm, more preferably larger than 12 mm, even more preferably larger than14 mm, yet more preferably larger than 15 mm, still more preferablylarger than 16 mm, yet still more preferably larger than 17 mm, yet evenmore preferably larger than 18 mm, still even more preferably largerthan 19 mm, most preferably larger than 20 mm, and smaller than 95 mm,more preferably smaller than 90 mm, more preferably smaller than 85 mm,even more preferably smaller than 80 mm, yet more preferably smallerthan 75 mm, still more preferably smaller than 70 mm, yet still morepreferably smaller than 65 mm, yet even more preferably smaller than 60mm, still even more preferably smaller than 55 mm, most preferablysmaller than 50 mm.

Preferably, said pickup coil comprises a maximal diameter which islarger than 10 mm, more preferably larger than 12 mm, even morepreferably larger than 15 mm, yet more preferably larger than 18 mm,still more preferably larger than 20 mm, yet still more preferablylarger than 22 mm, yet even more preferably larger than 24 mm, stilleven more preferably larger than 26 mm, most preferably larger than 28mm, and smaller than 70 mm, more preferably smaller than 65 mm, evenmore preferably smaller than 60 mm, yet more preferably smaller than 50mm, still more preferably smaller than 40 mm, yet still more preferablysmaller than 35 mm, yet even more preferably smaller than 30 mm, stilleven more preferably smaller than 25 mm, most preferably smaller than 20mm when said implant is in an expanded position.

Preferably, said heater coil comprises a length which is larger than 1mm, more preferably larger than 2 mm, even more preferably larger than 3mm, yet more preferably larger than 4 mm, still more preferably largerthan 5 mm, most preferably larger than 6 mm, and smaller than 30 mm,more preferably smaller than 27 mm, still more preferably smaller than25 mm, yet even more preferably smaller than 24 mm, still even morepreferably smaller than 22 mm, most preferably smaller than 20 mm.

Preferably, said heater coil comprises a maximal diameter which islarger than 2 mm, more preferably larger than 4 mm, even more preferablylarger than 6 mm, yet more preferably larger than 8 mm, still morepreferably larger than 10 mm, yet still more preferably larger than 12mm, yet even more preferably larger than 13 mm, still even morepreferably larger than 14 mm, most preferably larger than 15 mm, andsmaller than 90 mm, more preferably smaller than 80 mm, even morepreferably smaller than 70 mm, yet more preferably smaller than 60 mm,most preferably smaller than 50 mm when said implant is in an expandedposition.

Preferably, said implant comprises a distance between said pickup coiland said heater coil, said distance being larger than 1 mm morepreferably larger than 3 mm, even more preferably larger than 5 mm, yetmore preferably larger than 6 mm, still more preferably larger than 7mm, yet still more preferably larger than 8 mm, yet even more preferablylarger than 9 mm, still even more preferably larger than 10 mm, mostpreferably larger than 12 mm, and smaller than 80 mm, more preferablysmaller than 70 mm, even more preferably smaller than 60 mm, yet morepreferably smaller than 50 mm, most preferably smaller than 40 mm.

The present invention further provides a system for treating atrialfibrillation by multiple ablation of the inner walls of a pulmonary veinvia heating, comprising an implant comprising an electrical circuitcomprising a pickup coil, a heater coil and a temperature-controlledswitch as described in this text, and a magnetic field generator forgenerating a time-varying magnetic field at the position of the implantdevice, whereby preferably said magnetic field generator comprisesorientation means for changing the orientation of the magnetic fieldgenerated by said generator. “Changing the orientation of the magneticfield” hereby refers to a change in the polarization of the time-varyingmagnetic field and/or direction of propagation of accompanyingelectromagnetic waves. By using the orientation means, the generator canbe arranged to provide a magnetic field which varies in time maximallyalong a longitudinal axis of the pickup coil, thereby efficientlyinducing a current in said pickup coil. The orientation means maycomprise a movable and/or rotatable arm or antenna-like structure, suchas a U-shaped electromagnet. Preferably, said system comprises fourimplants such as disclosed here above.

In a similar aspect, the present invention provides a system fortreating atrial fibrillation by multiple ablation of the inner walls ofa pulmonary vein via heating, comprising an implant as disclosed in thisdocument, comprising a temperature-dependent LC-circuit, whereby said LCcircuit comprises a resonant frequency which is temperature-dependent; amagnetic field generator for generating a time-varying magnetic field atthe position of the implant device; a temperature measurement apparatusarranged for measuring said resonant frequency of said LC circuit andarranged for relating a measured resonant frequency to an implanttemperature; temperature controlling means arranged for:

-   -   receiving said implant temperature from said temperature        measurement apparatus;    -   comparing said implant temperature to a pre-determined ablation        temperature;    -   controlling the time-varying magnetic field generated by said        magnetic field generator on the basis of said comparison.

Preferably, said system comprises four implants such as disclosed hereabove.

In a further aspect, the present invention provides a method for thetreatment of a patient with atrial fibrillation by pulmonary veinisolation via ablation of a substantially complete circumferential bandon one or more pulmonary veins' inner walls, comprising the steps of

-   -   implanting one or more implant devices in one or more pulmonary        veins by means of a sheath and a guidewire, said implant devices        each comprising an ablation region along at least a portion of        their length, said ablation regions being adapted for surface        contact with said pulmonary veins and said ablation regions        subtending at least a substantially complete circumferential        band and being effective to ablate a signal-blocking path within        said pulmonary veins upon application of energy to said implant        devices;    -   retracting the sheath and guidewire;    -   subsequently heating the ablation region of the one or more        implant devices by external energy-providing means, which are        spatially separated from the implant device.

In a related aspect, the present invention provides a method fortreating atrial fibrillation by multiple ablation of the inner walls ofa pulmonary vein via heating, comprising the steps of:

-   -   implanting one or more implants as disclosed in the present        document, preferably comprising a pickup coil, a heater coil and        a temperature-controlled switch or preferably comprising a        temperature-dependent LC-circuit, whereby said LC circuit        comprises a resonant frequency which is temperature-dependent,        in one or more pulmonary veins;    -   applying a time-varying magnetic field at the position of said        implants, thereby heating up said one or more implants to a        pre-determined ablation temperature.

It should be stressed that in the above method, the heating of theimplant device occurs after the surgical procedure. This improves theease of the heating procedure and the comfort of the patient.

In a similar aspect, the present invention provides a method for heatingone, two or more implant devices, which are suitable to be implanted inone, two or more vessels, comprising the steps of:

-   -   subsequently positioning said implant devices in said vessels by        means of a sheath and a guidewire, said implant devices each        comprising an ablation region along at least a portion of their        length, said ablation region subtending at least a substantially        complete circumferential band or a substantially spiraling band,        said implant devices effective for ablating a signal-blocking        path within said vessels upon application of energy to said        implant devices;    -   retracting the sheath and guidewire;    -   heating the ablation region of said implant devices by external        energy-providing means which are spatially separated from said        implant devices characterized in that said heating occurs after        said sheath and guidewire are retracted and said heating of said        implant devices occurs simultaneously.

In a preferred embodiment of the method, a recovery period is observedprior to heating the ablation region of the one or more implant devicesby external energy-providing means. Furthermore, this recovery period islong enough to allow the one or more implant devices to be overgrown bybodily tissue. This recovery period may also be long enough to test ifthe implant devices are well positioned and do not move substantiallywithin the vessel.

The advantages of observing a waiting period are multiple: the patienthas time to recover from the surgical procedure, extra tests can beperformed during the waiting period to check whether the implant devicewas well implanted, bodily tissue can overgrow the implant device,thereby improving the contact of implant device with the vessel's innerwall and thus improving the efficiency of the ablation procedure, etc.

In a particular preferred embodiment of the method, the step of heatingthe ablation region of the one or more implant devices by externalenergy-providing means, which are spatially separated from the implantdevice, is performed repeatedly at well-spaced time-intervals.

The presented method has the main advantage that in case multipleablation procedures are necessary, no second surgical procedure isneeded, i.e. the implanted implant device or devices can be reused for asecond, third, . . . ablation procedure.

In a more preferred embodiment of the method, one or more implantdevices as described in this document are being used. Thereby theimplant devices can be engineered in order to produce the requiredeffects by engineering their shape, size, material composition, magneticand thermal properties, etc.

In a still more preferred embodiment of the method, use is made of asystem as described in this document. In this case, the implant devicecan be heated by the external energy-providing means and ahighly-controlled temperature of the ablation region of implant can bereached.

In a preferred embodiment, at least one implant device comprises a shapewhich is adapted for a pulmonary vein.

In a preferred embodiment, the vessels comprise one or more pulmonaryveins and said ablation regions of said implant devices are adapted forsurface contact with said pulmonary veins and subtending at least asubstantially complete circumferential band for ablating asignal-blocking path within said pulmonary veins upon application ofenergy to said implant devices. In a more preferred embodiment, theimplant devices are positioned at or near the antrums of the pulmonaryveins and/or the ablation regions of the implant devices are positionedsuch that they subtend essentially circumferential paths at or near theantrums of the pulmonary veins.

In an embodiment of the method, the patient's vessels into which animplant is to be implanted are scanned using a 3D scanning techniquesuch as CT or MRI to collect data on the varying diameter of the vessele.g. when going from the ostium to the antrum. From these data, one canderive the necessary shape and dimensions of the implants e.g. for allfour PVs of a patient. This measuring can be done without a surgicalprocedure, thereby increasing the patient's comfort and wellbeing andreducing medical risks. After this measuring, the implants can becustom-made to fit the patient's vessel or vessels. Obviously,custom-made implants, in contrast with standard-sized implants, increasethe success rate of any medical procedure.

The following test describes the system, device and method according toembodiments of the present invention as they are applied to and testedin the treatment of pigs.

Twelve pigs were anaesthetized following good animal practices. Aftercatheterizing the right atrium, and following successful transseptalpuncture, a guiding catheter is placed in the left atrium. In an orderfree to choice by the cardiologist, the four pulmonary veins areconsecutively engaged by the guiding catheter. Following this, a 0.014″guidewire is put distally into the pulmonary vein of choice. Apreselected (guided by preprocedural CT scan) implant device is thenpositioned into the antrum/ostium of the pulmonary vein. Uponcontrolling the exact position—using the five radioopaque markers on theimplant device—the self-expanding implant device is then released intothe antrum/ostium/pulmonary vein so as to have the four most proximalmarkers outside of the pulmonary vein, and only have the fifth mostdistal marker residing inside the pulmonary vein. This procedure isrepeated for the four different pulmonary vein ostia, so that at the endof the procedure all four implants are in situ. The procedure is thanterminated, all catheters are withdrawn, hemostasis is achieved, and theanimals are awakened.

An average of two weeks later (14+/−5 days) the animals are placedinside the dedicated magnetic field generator, using the predefinedprotocol to activate the implant devices.

The day after the implant activation, the animals are recatheterized,again with placing a guiding catheter transseptally into the leftatrium. Electrophysiology catheters are the placed inside the leftatrium so that signal mapping can be performed. A lasso catheter isplaced inside the pulmonary veins so that after stimulation completeentrance block is proved. Consequently, exit pacing is performed,proving no atrial capture from the pulmonary veins (showing exit block),so that finally (bidirectional) complete isolation is confirmed.

All procedures are successful, with complete isolation shown in 47/48pulmonary veins (98%). No side effects or complications are noted.

Anatomopathology shows good apposition in 46/48 cases. Transmurallesions are present in 43/48 (96%) cases.

The following describes another test of the system, device and methodaccording to embodiments of the present invention in the treatment ofswine.

Twenty domestic swine will be utilized, aged approximately 6 months andweighing about 75 kilograms (165 pounds). All animals will receiveacetylsalicylic acid 325 mg and a loading dose of clopidogrel 600 mg onthe day of the procedure. An MRI of the brain is made before theprocedure.

Anesthesia will be induced with ketamine 33 mg/kg and midazolam 0.5mg/kg supplemented with a 5-mg/kg ketamine bolus and a 0.25-mg/kgmidazolam bolus for intubation. Following intubation, anesthesia will bemaintained with isoflurane 1-3% and fentanyl 30-100 mcg/kg/h. Femoralarterial access will be obtained percutaneously for hemodynamicmonitoring. Lidocaine 2-4 mg/kg intravenous (IV) bolus followed by 50mcg/kg/min continuous IV infusion will be administered for prophylactictreatment for arrhythmias. Vital sign and ECG monitoring is performedcontinuously.

Bilateral femoral venous access will be achieved percutaneously, and two9-Fr 80-cm sheaths will be positioned in the heart under fluoroscopicguidance. IV heparin will be administered to achieve an activatedclotting time >250 s. An 8.5-Fr intracardiac echo (ICE) catheter will beintroduced to visualize anatomy and facilitate transseptal puncture.Double transseptal puncture will be performed, and the ICE catheter isplaced in the LA. A 14-Fr deflectable guide sheath will be introducedover an exchange wire through one of the 9-Fr sheaths. The guide sheathwill be advanced into each separate pulmonary vein (PV) sequentially.Angiograms of the different PV will be acquired through contrastinjection (if necessary using a 6F catheter). Subsequently PVelectrograms will be recorded with a multipolar circular electrodecatheter.

Using the PV angiograms as a guidance, the most appropriate size ofimplant will be selected. Ideally two devices are implanted in eachswine. Device size is selected as to exceed the natural diameter of thePV by 15-20%.

The deflectable guide sheath is aimed at the ostium of the selected PVand a new angiogram is made of the targeted vein. A second speciallydesigned deflectable 13-Fr sheath loaded with the device and a J-tiphydrophilic 0.016″ radio-opaque guide wire is prepared outside the bodyof the swine. The device is thoroughly flushed to make sure no air isleft inside the lumen of the sheath or inside the device. After havingverified no air is left inside the lumen, the 13Fr sheath, device andguidewire are introduced through the aforementioned sheath. The 13Frsheath is connected to a pressurized saline infusion and to a contrastinjection system. The guidewire is advanced deep into the selected PV. Anew angiogram of the PV is made by injecting contrast though the sheathwith the device. The sheath with the device are advanced into the PV asfar as the length of the selected device. Another angiogram is made inorder to verify the optimal position of the device. Now the device isslowly released into the lumen of the PV by pulling back the 13Frsheath. At the final moment before definitively releasing the device,the position is checked by an angiography and by push-and-pull on thedevice itself that is already partially in place. Only after havingverified that the device is in the optimal position, the release systemof the device is activated, the device fully deploys into the vein andthe 13Fr sheath is pulled back and removed from the body after havingmade one final angiogram.

After having implanted the desired number of devices, the magnet isinstalled making sure the swine heart is in the target zone. Aspecifically designed thermometer is placed adjacent to the devicethrough the 14Fr sheath. The magnet is activated using the predefinedsettings (Amplitude, Frequency, Duration). The ICE catheter continuouslymonitors the production of micro-bubbles in the left atrium.

After completion of vein ablation, the multipolar circular electrodecatheter is returned to the veins and PV electrograms will again berecorded and compared to the original electrograms before ablation. Exitpacing from the circular electrode catheter is performed to provebidirectional block. New angiograms will be acquired at this stage.

Catheters will be removed and ten acute animals will be sacrificed withan overdose of barbiturates. Ten chronic animals will be recovered andgiven aspirin 325 mg and clopidogrel 75 mg daily and will be sacrificed30 days post procedure. A postmortem median sternotomy will beperformed, and the lungs and heart will be removed from the chest. Thelungs will be carefully dissected free from the heart, with effort tokeep the PVs intact. The LA will be opened along the roof and grosslyinspected. A tissue block containing each PV will be dissected from theLA. The veins containing the devices will be then sectionedcircumferentially for histopathological examination. The PV tissueblocks will be fixed in formalin and then stained with hematoxylin andeosin, Movat's pentachrome, and Masson's trichrome stains.

The invention is further described by the following non-limitingexamples which further illustrate the invention, and are not intendedto, nor should they be interpreted to, limit the scope of the invention.

Examples

FIG. 1 represents a preferred embodiment of an implant 1 according tothe present invention with circular cross-section (FIG. 1B) and ellipticcross-section (FIG. 1C). It should be clear that in the other figuresshowing embodiments of implants, the cross-sections can also be circularor elliptical, or basically any other shape which fits the vessel intowhich it is to be implanted best.

The represented implant 1 comprises a body 2, in this case shaped asnarrowing tubular cage and made of metal wires 3 or the like, suitableto be placed inside the antrum of a pulmonary vein.

More in particular, the body 2 is provided of in this case threecircular wires, a first bigger circular wire 4, an intermediatemid-sized second circular wire 5, and a third smaller circular wire 6.

The outlook of the body 2 may though be provided of more or less thanthree rings, for example two to five, more specifically three to four,or even more than five rings.

The first bigger circular wire 4 is connected with the intermediatemid-sized second circular wire 5 by means of in this case three straightinclined but upstanding wire portions 7.

In a similar manner, the intermediate mid-sized second circular wire 5is connected with the third smaller circular wire 6 by means of in thiscase also three straight inclined but upstanding wire portions 8.

The wire portions 8 are here located at intermediate positions withrespect to the wire portions 7.

The result is a narrowing tubular cage, which could also be described asa mainly conical or funnel shaped body 2, provided of three circularwires positioned at a distance from each other, at least when the body 2is in a released or not compressed position.

In general terms, the self-expanding body 2 is preferably provided of ashape that fits the anatomy of the vein, for example a pulmonary vein.

The circular wires may, according to a preferential embodiment, beprovided of a mainly oval shape such that the body 2 is built up ofdifferent oval rings of converging diameter, ideally adapted to theanatomy of the pulmonary veins.

These rings of the body 2 will typically range in diameter from 3 to 30mm, more specifically between 5 mm and 20 mm, even more specificallybetween 9 mm and 13 mm if to be implanted in the heart, morespecifically in the atria, more specifically in the left and rightatrium, more specifically in the antrum or ostium of the pulmonaryveins.

These rings of the body 2 will typically range from 5 mm to 50 mm, morespecifically from 8 mm to 40 mm, even more specifically between 10 mmand 30 mm if to be implanted at the site of the antrum.

The body 2 has self-expanding properties thanks to the elasticcharacteristics of the material used, and thanks to the geometry of thebody 2.

If a metal is used, it may be nitinol-based known for its superiorself-expansion properties.

The self-expanding body 2 is conceived to stop expanding when itencounters a pressure of about 1 to 150 mm Hg, more specifically 3 to 80mm Hg, more specifically 5 to 60 mm Hg, more specifically 10 to 40 mmHg, equal to the distension pressure needed to alter the left atrium'sanatomy.

Alternatively, a self-expanding cage may be conceived existing ofdifferent circular or oval shape rings that are interconnected. Therings may be formed so that a spiral form is created. The differentrings of the spiral will also be interconnected so that upon heating orupon release of substances from the cage, no openings for recurrence ofelectrical signals are left open.

In this case, the material used is of the type that reacts, for exampleheats, in response to a remote applied alternating magnetic field.

The principle of hysteresis causes the metal of the cage to heat up,depending on the absorptive properties of the metal alloy that builds upthe body 2.

Alternative is an electromagnetic field generator that changes polarityand therefore induces hysteresis heating in materials put inside thefield. The system may use the Curie temperatures (the temperature towhich a certain material can be heated, upon which further energydelivery does no longer change the temperature) that certain materialspossess, as to the target temperature that should and can be reached.For example, ZnFe₂O₄ is a material that has a Curie temperature between30 and 45 degrees Celsius.

A metal alloy cage that comprises ZnFe₂O₄ in its structure may thereforebe heated to exactly 45 degrees, close to the target temperaturedesirable for appropriate ablation purposes.

Another alternative to deliver energy to the cage could be directinduction, using a magnetic core, again making use of hysteresis heatingbut in a more directive way.

Another alternative to deliver energy to the cage could be to useelectromagnetic radiation through a thermical chemical-release systemwith external trigger, where the chemical is only released on demand andat the appropriate sites.

It is clear that still alternative energy field can be applied, such aselectromagnetic radiation, hysteresis heating, reaching Curietemperature, direct induction, thermal/chemical release system,mechanical/chemical release system, indirect induction, Joule heating,acoustic energy, mechanical vibration, chemical release system.

Alternatively, the body 2 can be provided of toxic substances that areonly released upon introduction into the pulmonary vein/antrum, forexample after applying an external energy field, which toxic substancesthen produce a lesion of limited necrosis/neurotoxicity.

In FIG. 2, an alternative embodiment of the implant 1 according to theinvention is represented.

The body is built up out of braided metal wires 9 that have multipleinterconnections, crossings and layers. This iteration allows fornumerous connections with the atrial vascular or other wall.

In FIG. 3, the implant 1 is conceived as a spirally shaped wire 10 ofwhich the diameter gradually goes down along its longitudinal axis.

The windings 10A-10D, in this case four, are mutually connected withbridging upstanding wire portions 8.

This embodiment thus differs from the embodiment as represented in FIG.1 by the single or continuous spirally shaped wire instead of thedifferent circular wires 4-6.

The bridging upstanding wire portions 8, apart from giving structure andstrength to the implant 1, also provide closed loops.

Indeed, the different windings 10A-10D are still interconnected toensure, once the device is released, full and circular lesions in theheart, more specifically in the atria, more specifically in the left andright atrium, more specifically in the antrum or ostium of the pulmonaryveins.

In FIG. 4 the implant shows longitudinal metal beads 11 that are outwardbending, and that still show several interconnections between them, toultimately form a metal cage.

An implant 1 according to the present invention may comprise portionsmade of different metal alloys with optionally different ferromagneticproperties and/or absorption coefficients, with specific response toalternating magnetic fields.

Alternatively, the basic structure of the implant 1 may be made of oneand the same material, which may be provided of coating portions withvarying properties.

The embodiment illustrated in FIG. 5 shows an implant conceived as aspirally shaped wire 10 of which the diameter gradually goes down alongits longitudinal axis, but where, as opposed to the embodimentrepresented in FIG. 3, the windings 10A-10E, in this case five, aremutually connected by means of bridging upstanding wires 12 which reachfrom the biggest winding 10A up till the smallest winding 10E.

The biggest winding 10A of the implant 1 is built up of a metallic alloywith self-expanding properties, and covered with a layer of a metal thathas minimal ferromagnetic properties 100.

The next winding 10B is built up of the same self-expanding alloy,covered with a layer of material that has a higher rate of absorption ofenergy during the hysteresis phenomenon, and thus with altering magneticfields will reveal different thermal heating properties 200.

The windings 10D and 10E most distal from the biggest winding 10A, to belocated in a portion of the pulmonary vein remote from the heart, isprovided of a layer of material that has still a higher rate ofabsorption of energy during the hysteresis phenomenon 400.

According to another embodiment of the implant 1, a portion of which isschematically represented in FIG. 6, the wire building up the body 2 ofthe implant 1 is composed of different layers, in this case three layersmade of different alloys 15, 16 and 17.

These different alloys are in contact with each other, and depending ondifferent magnetic fields to be applied, they will exhibit differentproperties.

It is clear that alternatively or in combination with the above or otherfeatures, one or more layers can have high thermal isolationcharacteristics, in order to direct heat where needed, and to isolateportions to prevent undesired heating of blood or tissue.

According to another embodiment of the implant 1, a portion of which isschematically represented in FIG. 7, the body 2 is provided ofmicropores 18 at the abluminal side 13 (in contrast with the adluminalside 14) wherein substances are provided.

Such substances may for example be a selection or a composition of oneor more of the following substances:

-   -   ethanol;    -   tetrodotoxin and batrachotoxin;    -   maurotoxin, agitoxin, charybdotoxin, margatoxin, slotoxin,        scyllatoxin or hefutoxin;    -   calciseptine, taicatoxin, calcicludine, or PhTx3;    -   botulinum toxide;    -   cytochalasin D, rapamycin, sirolimus, zotarolimus, everolimus,        paclitaxel;    -   glutamate;    -   isoquinoline;    -   N-methyl-(R)-salsolinol;    -   Beta-carboline derivates.

The micropores 18 are closed when the body is coiled together, forexample prior to the provision in a guiding catheter system, and uponrelease into its site of destination, upon expansion, these micropores18 open so that the substances inside the metal arms of the cage can bereleased.

According to another embodiment of the implant 1, a portion of which isschematically represented in FIG. 8, the body 2 is covered by athermoactive coating 19 which is only activated upon temperatures above35° C. so that the body temperature would trigger activation.

Alternatively, a thermoactive coating 19 can be provided which is onlyactivated upon temperatures above 45° C. so that an external applicationof an energy field would trigger activation.

Alternatively, an insulating material 44 can be provided at the parts ofthe implant which comes into contact with parts of the body which arepreferably not heated such as some parts of the vessel wall or theblood. Hereby the parts of the implant which are heated are thermallyinsulated from e.g. the blood.

The energy field could for example be a remote applied alternatingmagnetic field, heating the body 2 of the implant 1 thanks to ahysteresis effect.

At the said activation temperature, the coating 19 gets absorbed, andthe active component that is residing below the coating 20 is releasedinto the vascular wall.

Note that the elongated shape and/or the expanding forces provide can beconsidered as anchoring means of the implant 1.

Alternatively, hooks or barbs or the like 29 can be provided as in FIG.11 on the outwardly directed portions of the implant 1, providingguaranteed anchoring of the implant 1 once it put in place.

According to still another embodiment, the outer rings or other cagestructures that are fitted into the antrum, or the whole cage may beequipped with structures to increase the solidity of cage immobility, toascertain the fixed position of the implant, to reduce the possibilityof movement of the implant after the implantation.

The method of placing the implant is easy and can be performed ashereafter described.

According to the known practices, a catheter 30 with guidewire 31 isintroduced up till the place where the implant 1 is to be left. This isshown schematically in FIGS. 12 and 13.

Pull-back of the catheter while leaving the implant 1 in position causesthe implant 1 to expand.

As the shape and/or elastic characteristics of the implant 1 is/aresuitably adapted to fit and optionally press against the arterial orvenous structure, for example in the pulmonary vein, the implant 1 isleft in a safe and self-anchoring manner.

After full pullback of the catheter, the implant 1 is fully released.

Alternatively, the well-known balloon expansion can be applied.

An appropriate period can be awaited prior to applying an externalenergy field in order to trigger the triggerable portions of the implant1.

Various consecutive treatments by simply applying an appropriate energyfield can be considered, without the need to perform renewed invasivesurgery, which is the main advantage of the implant and the systemaccording to the present invention.

Furthermore, in case where the implant 1 is provided of varyingsubstructures, each with their own response to an externally appliedenergy field, varying treatments can be considered, for example withincreasing intensity.

Each portion can for example be triggered with a remote appliedalternating magnetic field characterized with a specific frequency.

It is clear that when reference is made to lesions, these may concerntransmural lesions extending up till the exterior wall, and that lesionsmay be continuous, as opposed to discrete or composed partial lesions.In fact, when the invention disclosed in this text is used for thetreatment of AF by PVI, it is preferable that the lesions are continuousand thus form a substantially circumferential band around the vessel'swall, thereby electrically isolating the PV(s) from the left atrium.

The present invention is by no means limited to the embodimentsdescribed by way of example and represented in the accompanyingdrawings; on the contrary, such an implant and system of an implant andexcitation device for the treatment of arterial and venous structuresaccording to the invention can be made in all sorts of shapes anddimensions while still remaining within the scope of the invention.

FIG. 9 shows a circular braided implant 21 in which one circumferentialregion 22 comprises an alloy with a specific Curie temperature and inwhich a second circumferential region 23 comprises an alloy with anotherspecific Curie temperature.

FIG. 10 shows a funnel-shaped braided implant 24 in which onecircumferential region 25 comprises an alloy with a specific Curietemperature, in which a second circumferential region 26 comprises analloy with another specific Curie temperature, and in which a thirdcircumferential region 27 comprises an alloy with still another specificCurie temperature.

FIG. 11 shows a funnel-shaped braided implant 28 with anchoring means 29in the form of small barbs.

FIG. 13 shows how the catheter 30 can be guided through the insertionvein 34, through the right atrium 36, though a hole to the left atrium35 to the pulmonary vein 37. In detail, the ostium 38 and antrum 39 ofthe PV is indicated.

FIG. 14 represents an embodiment of the external energy-providing means42 as it can be used for treating a patient during the ablationprocedure 43.

FIG. 15 shows an implant in place 40 and the ablation region in crosssection 41 in the antrum of the PV.

FIG. 18 shows another embodiment of an implant which has an hour-glassshape 45, whereby near the middle region, where the diameter becomessmaller, a set of heating rings 46 is attached around the hour-glassshaped part of the implant. The heating rings are attached to thehour-glass shaped part in a thermally insulating manner such that littleheat is transferred to the blood stream when the heating rings areheated. Furthermore the heating rings are meant to be completelyseparated from this blood stream, since the hour-glass shaped part maybe covered by a blood-tight tissue and may be clamped into the vessel ator near the implant ends 47 and 48.

FIG. 19 shows an embodiment of an implant comprising a fuse, so that atcertain temperatures, more specific the temperature that is reached toachieve an optimal ablation, between 40 and 80 degrees Celsius, morespecifically between 45 and 60 degrees Celsius, the circuit that may begenerated gets interrupted.

This comes from the phenomenon that when an implant, more specifically ametallic implant, more specifically a nitinol implant is brought intothe alternating magnetic field, an electrical current is generatedthrough the metal implant itself, thus generating accelerated heating byitself (induction and Joule heating). This phenomenon results inextremely rapid heating of the implant, that can be stopped byinterrupting the electrical current that may run through the implant.This stopping of the current may be caused by a fuse that is mountedwithin the metallic implant, and that for instance may exist of aresistance, that breaks when it is heated above a certain temperature.In this case, the fuse would stop heating up further above a temperatureof 45-60 degrees, more specifically 50-55 degrees. FIG. 19 a shows adetailed view of the fuse.

In a different configuration, as shown in FIG. 20, the metal implant canbe build up of memory shape alloys, so that upon heating of the device,the different metallic parts take up another configuration, therebyinterrupting the electrical current that can run through the implant.Details of the on and off position of the switch or fuse are shown inFIGS. 20 a and 20 b respectively. This different, i.e. open,configuration consists potentially of the original form of the metal, sothat it goes back to its “memory shape”. This is called a “shape memorymetal”.

In a still different configuration as shown in FIG. 21 and a detail inFIG. 21 a, the implant consists of two different materials, where uponheating the bondage between the two different metals gets interrupted,so to stop the electrical current from running through the implant.

Another addition of this application is that the heating needs to beunidirectional. The blood needs to be isolated from the heating becauseof two reasons: first, blood should not be heated because proteins inthe blood can denature and form clots, and second, because blood is ahuge heat dissipator that may substract too much heat away from theimplant, it would need too much energy to get the ablation region of theimplant to the desired temperature. Therefore, an extensive coating isformed around the implant, but almost exclusively on the ADLUMINAL sideas illustrated in FIG. 22, so that when the implant is heated, no heatis dissipated towards the blood stream.

FIG. 23 illustrates the concept of the present invention whereby animplant device (55) is provided with a built-in thermal switch (54).Hereby, said implant may be activated by applying a time-varyingmagnetic field φ, e.g. a radiofrequent field as can be produced by anelectromagnet or electromagnetic coil or antenna (51). Said time-varyingmagnetic field φ may induce a current in said electrical circuit,through said pick-up coil (53) and said heating coil (52), if saidswitch (54) is closed. Whether the switch is closed or open, depends onthe temperature at the position of the switch or at a position of atemperature sensor attached to said switch, preferably via a thermostat.

FIG. 24 illustrates the dimensions of an implant in an expanded positionin a vessel. Hereby, the vessel (65) is typically between 5 mm and 50 mmwide, e.g. 20 mm in diameter. The heater coil (62) can be about 20 mmlong, while the pickup coil (63) can be, and preferably is, longer than20 mm. The thermal switch (64) in FIG. 24 is positioned near the heatercoil (62) and is open or closed depending on the temperature at or nearsaid heater coil. The heater coil subtends a circumferential ablationregion of the vessel over the heater coil length.

FIGS. 25 a-g illustrate different embodiments of the present invention,whereby the shape and absolute and relevant sizes of the coils maydiffer between different embodiments. A heater coil (72) and a pickupcoil (73) can be clearly identified, the pickup coils (73) as presentedcomprising a large amount of windings to increase their inductances. Athermal switch (74), in FIGS. 25 a-e attached to a printed circuit boardand coated, is coupled to heater coil (72) and pickup coil (73). InFIGS. 25 d-g, a pcb (75) comprising one or more electronic circuitry,possibly including a thermal switch and/or a supply circuit coil iscoupled to the pickup coil (FIG. 25 f-g) or switch (FIG. 25 d-e). Theshape of the coils can be arranged to fit into a specific vessel, e.g. acylindrical vein or artery (FIG. 25 a) or a cone-shaped vein or artery(FIG. 25 b-g). In particular for pulmonary veins, a cone-shaped heatercoil for implantation in the ostium (FIG. 25 b, 25 d, 25 g) ispreferred.

A winding of the heater coil (76) induces a temperature profile (77) inthe wall (78) of the vessel upon activation of the implant. This isillustrated in FIG. 26, where it is illustrated that the heat isdeposited mainly near the winding, but that it is possible that also theouter side of the vessel (79) can be heated to an increased temperature.Appropriate modelling of the vessel and testing of the setup allows toset the optimal temperature for the implant to ablate a signal-blockingpath on the inner wall of the vessel, without unnecessary damagingtissue which should remain intact.

Further embodiments comprising e.g. a PTC (80) or thermistor switch, areillustrated in FIGS. 27 a-b for essentially cylindrical implants.

In some embodiments, it is necessary or advisable to use electricalcomponents which need DC current or voltage to operate. In suchembodiments, it is necessary that the implant comprises an AC-DCconverter in order to convert AC current flowing via induction in atleast part of the circuitry of the implant, to DC current. Thisconverter may obtain an AC input current from the pickup coil or from asupply circuit coil. Such a converter may be part of a larger electroniccircuit which can be attached to a pcb (81) and coupled to the coils asillustrated in FIG. 28.

FIGS. 29 a-d illustrate electronic circuits which can be used inembodiments of the implant of the present invention. If a large currentis sent through a heater wire or heater coil, the heater coil generatesheat and the temperature around the heater coil rises. If there is nocurrent through the heater coil, the temperature drops because ofcooling inside a bloodstream. For ablation, a target temperature around55° C. may need to be reached and held for an amount of time. A digitalthermostat PCB (IC1) measures the temperature by means of a temperaturesensor and switches the large current through the heater coil on or offby means of a switch (IC3), hereby forcing the temperature around theheater coil to rise or drop. The heater coil is powered by means of theenergy induced in a large pickup coil. The control circuit is powered bya separate coil.

The temperature sensor measures the internal temperature and compares itto 55° C. with a hysteresis loop of 2° C. This chip provides a highoutput voltage level (5 V) if the measured temperature is higher than55° C., and a low output voltage level (0 V) if the temperature is lowerthan the target temperature of 55° C. This thermostat chip (IC1) is usedto control a switch (IC3), which in this case is a solid-state relay(SSR) with integrated optocoupler, as this SSR is able to switch thealternating current induced by the pickup coil. As this switch (IC3)requires a larger current than the temperature sensor can provide (thethermostat chip may have a very low output current driving capability),a buffer needs to be used. As a high switch input voltage results in aclosed state and a low voltage results in an open state, this buffer isrealised by means of an inverter (IC2) with large output current. Aresistor (R1) of e.g. 330 Ohm between switch (IC3) and inverter (IC2)limits the switch drive current, hereby protecting the switch input.This chain (FIG. 29 b) provides the temperature control. As this chainconsists of active devices, this can only work if adequately supplied.The chain in FIG. 29 a provides a stable 5 V supply voltage out of aninput AC-voltage delivered by a separate circuit supply coil. This coilprovides a lower AC-voltage than required for the power chain. The inputAC-voltage is transformed into a DC-voltage by a half-wave rectifier(D1) higher than the target 5V. Then a 5V linear regulator (IC4) is usedto transform this voltage into a stable 5 V power supply. Thecapacitors, e.g. of 100 nF, visible throughout the design are placed fordecoupling (local stabilization of the supply voltage).

The symbols GND, VAC and 5V each represent a net, connecting the symbolswith the same name. These have no physical meaning other than justanother connection. GND is the universal sign for a voltage reference(as all voltages need to be referred to some point inside a circuit).This is not to be mistaken for an earth connection. GND is often chosento be a connection with very low impedance, and therefore often realizedas reference plane.

The connector CON1 is the interface for the heater coil (pin 1), thecircuit supply coil (pin 2) and the voltage reference GND (pin 3).

Another embodiment of the electrical circuitry is illustrated in FIGS.29 c-d. This board is a smaller version as the one presented in FIGS. 29a-b. The functionality remains identical, but it uses smallercomponents. The regulator (IC4) is different and the switch and resistorare combined into one component (IC3). Also the large connector ischanged into three smaller connectors CON1-CON3. The extra connectorsCONVCC, CONGND and CONTout can be used to split the board into a smallboard with a temperature sensor and another board with the remainder ofthe chips. This way, the small temperature sensor can be brought muchcloser to the heater coil.

In FIGS. 29 a-d, embodiments of an implant according to the presentinvention are illustrated, whereby the implants comprise a separatesupply coil with a dedicated supply circuit for providing the othercomponents such as the thermostat, inverter and switch with a constantDC voltage of e.g. 5V, as illustrated in FIG. 29 e. In other embodimentsof an implant according to the present invention, a center tap may beused at the pickup coil side to obtain the circuit power instead of aseparate circuit power supply coil (FIG. 29 f). This seems easier tointegrate in an implant instead of using a third coil. This latterembodiment may pose the following extra problem: The center tap may besituated inside the switching chain. If a large current is flowingthrough the coil combination, this current generates a magnetic fieldcounteracting the external magnetic field that actually caused thiscurrent to flow. This results in a voltage drop across the coilterminals. This means that in case of a closed switch, the voltageacross the coil terminals can be much lower than in case of an openswitch. This voltage difference could cause regulators to fail due tohigh power dissipation. To solve this problem, extra components need tobe added to the circuit to prevent this. Such components may be added ine.g. a miniaturised chip design.

FIGS. 30 a-34 illustrate embodiments of external energy providing meanswhich can be used in a system or method of the present invention forproviding energy to the implant by providing a time-varying magneticfield at the position of the implant.

FIGS. 30 a-b and also FIGS. 33-34 illustrate an embodiment whereby apatient with an implant may sit down during the heating procedure, as atime-varying magnetic field is produced preferentially within thearc-shaped arms (90) of the generator (91). The arms are capable ofbeing rotated, preferably around a horizontal axis (92) and the patientchair (93) may also be rotated, preferably around a vertical axis, andmay be moved up and down, such that an optimal induction couplingbetween magnetic field of the generator and induced field in the implantis reached. The optimal position of the generator may depend on thepatient, and on the orientation of the treated vessels in the patient.Therefore a generator as illustrated in these figures, whereby both theorientation and magnitude of the magnetic field may be varied in time,is particularly preferred in the systems and methods presented in thisdocument.

FIG. 31 illustrates the possibility of using a large magnetic fieldgenerator (91) around a table (94) onto which a patient can lie down fortreatment. The table can move horizontally through the generator.

FIGS. 32 a-b illustrate a magnetic field generator (91) which is capableof generating fields in different orientations, whereby the orientationwhich is optimal for inducing a current in the implant can be adapted ina patient-dependent manner.

It is supposed that the present invention is not restricted to any formof realization described previously and that some modifications can beadded to the presented example of fabrication without reappraisal of theappended claims. For example, the present invention has been describedreferring to PVs, but it is clear that the invention can be applied toother vessels for instance.

The present invention concerns, but is not limited to:

-   -   1. Method for heating one, two or more implant devices which are        suitable to be implanted in one, two or more vessels, comprising        the steps of:        -   subsequently positioning said implant devices in said            vessels by means of a sheath and a guidewire, said implant            devices each comprising an ablation region along at least a            portion of their length, said ablation region subtending at            least a substantially complete circumferential band or a            substantially spiraling band, said implant devices effective            for ablating a signal-blocking path within said vessels upon            application of energy to said implant devices;        -   retracting the sheath and guidewire;        -   heating the ablation region of said implant devices by            external energy-providing means which are spatially            separated from said implant devices    -    characterized in that said heating occurs after said sheath and        guidewire are retracted and said heating of said implant devices        occurs simultaneously.    -   2. Method according to point 1, whereby at least part of each of        said implant devices is made from at least one material which        shows magnetic hysteresis, such as a ferromagnetic,        ferrimagnetic or anti-ferromagnetic material.    -   3. Method according to point 2, whereby said implant devices        comprise a ferrous fluid.    -   4. Method according to any of the points 1 to 3, whereby heating        occurs by external energy-providing means which create a        time-varying magnetic field at the position of said implant        devices.    -   5. Method according to any of the points 1 to 4, whereby at        least one of said implant devices comprises a thermoactive        coating comprising an activation temperature between 35° C. and        37° C. so that the body temperature would trigger activation.    -   6. Method according to any of the points 1 to 4, whereby at        least one of said implant devices comprises a thermoactive        coating comprising an activation temperature above 45° C. so        that activation is triggered only when said ablation region is        heated by said external energy-providing means.    -   7. Method according to any of the points 1 to 6, whereby said        implant devices comprise substances capable of producing a        lesion of limited necrosis and/or neurotoxicity.    -   8. Method according to point 6, whereby at least one of said        implant devices comprises cavities which are filled with said        substances and which open when the implant is heated.    -   9. Method according to any of the points 6 to 8, whereby at        least two substances are mixed before being released, e.g. to        deliver a two-component neurotoxine.    -   10. Method according to any of the points 6 to 9, whereby said        substances are a selection or a composition of one or more of        the following substances:    -   ethanol;    -   tetrodotoxin and batrachotoxin;    -   maurotoxin, agitoxin, charybdotoxin, margatoxin, slotoxin,        scyllatoxin or hefutoxin;    -   calciseptine, taicatoxin, calcicludine, or PhTx3;    -   botulinum toxide;    -   cytochalasin D, rapamycin, sirolimus, zotarolimus, everolimus,        paclitaxel;    -   glutamate;    -   isoquinoline;    -   N-methyl-(R)-salsolinol;    -   Beta-carboline derivates.    -   11. Method according to any of the points 1 to 10, whereby at        least one implant device comprises a shape which is adapted for        a pulmonary vein.    -   12. Method according to any of the points 1 to 11, whereby said        vessels comprise one or more pulmonary veins and whereby said        ablation regions of said implant devices are adapted for surface        contact with said pulmonary veins and subtending at least a        substantially complete circumferential band for ablating a        signal-blocking path within said pulmonary veins upon        application of energy to said implant devices.    -   13. Method according to any of the points 1 to 12, whereby a        recovery period is observed prior to heating the ablation region        of the one or more implant devices by external energy-providing        means, whereby said recovery period is long enough to allow the        implant devices to be incorporated into the vessel's wall.    -   14. Method according to any of the points 1 to 13, whereby the        step of heating the ablation region of the implant devices by        external energy-providing means, which are spatially separated        from the implant device, is performed repeatedly at well-spaced        time-intervals.    -   15. A self-expanding implant device adapted to be implanted and        deployed within a vessel, said implant comprising an ablation        region along at least a portion of its length, the ablation        region being adapted for surface contact with the vessel and for        subtending at least a substantially complete circumferential        band or a spiraling band and said ablation region effective to        ablate a signal-blocking path within the vessel upon application        of energy to the implant device.    -   16. An implant according to point 15, whereby said ablation        region comprises at least one material which shows magnetic        hysteresis, such as a ferromagnetic, ferrimagnetic or        anti-ferromagnetic material.    -   17. An implant according to point 16, whereby said implant        devices comprise a ferrous fluid.    -   18. An implant according to any of the points 15 to 17,        comprising a thermoactive coating comprising an activation        temperature between 35° C. and 37° C. so that the body        temperature would trigger activation.    -   19. An implant according to any of the points 15 to 17,        comprising a thermoactive coating comprising an activation        temperature above 45° C. so that activation is triggered only        when said ablation region is heated by said external        energy-providing means.

20. An implant according to any of the points 15 to 19, comprisingsubstances capable of producing a lesion of limited necrosis and/orneurotoxicity.

-   -   21. An implant according to point 20, comprising cavities which        are filled with said substances and which open when the implant        is heated.    -   22. An implant according to any of the points 20 or 21, whereby        said substances are mixed before being released, e.g. to deliver        a two-component neurotoxine.    -   23. An implant according to any of the points 20 to 22, whereby        said substances are a selection or a composition of one or more        of the following substances:        -   ethanol;        -   tetrodotoxin and batrachotoxin;        -   maurotoxin, agitoxin, charybdotoxin, margatoxin, slotoxin,            scyllatoxin or hefutoxin;        -   calciseptine, taicatoxin, calcicludine, or PhTx3;        -   botulinum toxide;        -   cytochalasin D, rapamycin, sirolimus, zotarolimus,            everolimus, paclitaxel;        -   glutamate;        -   isoquinoline;        -   N-methyl-(R)-salsolinol;        -   Beta-carboline derivates.    -   24. An implant according to any of the points 15 to 23,        comprising a shape which is adapted for a pulmonary vein.    -   25. An implant according to point 24, whereby said ablation        region of said implant device is adapted for surface contact        with said pulmonary veins and for subtending at least a        substantially complete circumferential band.    -   26. An implant according to any of the points 15 to 25,        comprising a maximal circumference and a minimal circumference        and a ratio between maximal and minimal circumference, whereby        said ratio is smaller than 7 and larger than 3.    -   27. An implant according to any of the points 15 to 26,        comprising a variable circumference along a longitudinal        direction of the implant, said circumference varying between at        least 36 mm and at most 250 mm.    -   28. An implant according to any of the points 15 to 25,        comprising an essentially cylindrical shape comprising a        diameter which is at least 5 mm and at most 10 mm.    -   29. An implant according to any of the points 15 to 28,        comprising a distal portion and a proximal portion, whereby said        ablation region is located within 50% of the implant's total        length from the proximal portion.    -   30. An implant according to any of the points 15 to 29,        comprising a distal portion and a proximal portion, whereby said        ablation region is located within 15 mm from the proximal        portion.    -   31. An implant according to any of the points 15 to 30,        comprising a distal portion and a proximal portion, and        comprising an anchoring device connected to the ablation region        of said implant via a thermally insulating connection for        preventing overheating of said anchoring device, whereby said        anchoring device is connected to the distal portion.    -   32. A system comprising one, two, three, four or more implant        devices according to any of the points 15 to 31.    -   33. A system according to point 32, comprising external        energy-providing means, which are spatially separated from said        implant devices and able to provide energy to said implant        devices for increasing the temperature of the ablation regions        of the implant devices up to an ablation temperature.    -   34. A system according to any of the points 32 or 33, comprising        -   a sheath suitable for transporting and delivering the one or            more implant devices to or near the desired position in the            one or more vessels; and        -   a guidewire suitable for sequentially guiding the sheath            with the one or more implants to the desired position in the            one or more vessels.    -   35. A system according to any of the points 32 to 34, comprising        one, two, three or four implant devices according to any of the        points 15 to 31, each of which adapted for a corresponding        pulmonary vein.

1. Implant for treating atrial fibrillation by multiple ablation of theinner walls of a pulmonary vein via heating, comprising an electricalcircuit comprising a pickup coil, a heater coil and atemperature-controlled switch which comprises a closed position and aninterrupted position, said pick-up coil arranged for inducing anelectrical current through at least part of said electrical circuit towhich it is connected under the influence of a time-varying magneticflux through said pickup coil, wherein said heating coil is arranged forsubtending a substantially complete circumferential ablation region in apulmonary vein vessel, for obtaining a substantially completecircumferential signal-blocking lesion on the inner wall of said vessel,and wherein said switch is arranged to change from said closed to saidopen position when a temperature at or near said implant is higher thana pre-defined ablation temperature.
 2. Implant according to claim 1,wherein said implant is at least partly self-expanding.
 3. Implantaccording to claim 1, comprising a cone-like shape for implantation intothe antrum of a pulmonary vein.
 4. Implant according to claim 1, whereinsaid pickup coil comprises a length which is larger than 15 mm andsmaller than 75 mm.
 5. Implant according to claim 1, wherein said pickupcoil comprises a maximal diameter which is larger than 10 mm and smallerthan 60 mm when said implant is in an expanded position.
 6. Implantaccording to claim 1, wherein said heater coil comprises a length whichis larger than 3 mm and smaller than 25 mm.
 7. Implant according toclaim 1, wherein said heater coil comprises a maximal diameter which islarger than 10 mm and smaller than 70 mm when said implant is in anexpanded position.
 8. Implant according to claim 1, comprising adistance between said pickup coil and said heater coil, said distancebeing larger than 5 mm and smaller than 50 mm.
 9. System for treatingatrial fibrillation by multiple ablation of the inner walls of apulmonary vein via heating, comprising: one or more implants accordingto claim 1; a magnetic field generator for generating a time-varyingmagnetic field at the position of the implant device.
 10. Systemaccording to claim 9 wherein said magnetic field generator comprisesorientation means for changing the orientation of the magnetic fieldgenerated by said generator.
 11. System according to claim 9, comprisingfour implants.
 12. Implant for treating atrial fibrillation by multipleablation of the inner walls of a pulmonary vein via heating, comprisingan electrical circuit comprising a pickup coil, a heater coil and atemperature-dependent LC-circuit, wherein said LC circuit comprises aresonant frequency which is temperature-dependent.
 13. Implant accordingto claim 12, comprising a cone-like shape for implantation into theantrum of a pulmonary vein.
 14. System for treating atrial fibrillationby multiple ablation of the inner walls of a pulmonary vein via heating,comprising: an implant according to claim 12, comprising an electricalcircuit comprising a pickup coil, a heater coil and atemperature-dependent LC-circuit, wherein said LC circuit comprises aresonant frequency which is temperature-dependent; a magnetic fieldgenerator for generating a time-varying magnetic field at the positionof the implant device; a temperature measurement apparatus arranged formeasuring said resonant frequency of said LC circuit and arranged forrelating a measured resonant frequency to an implant temperature;temperature controlling means arranged for: receiving said implanttemperature from said temperature measurement apparatus; comparing saidimplant temperature to a pre-determined ablation temperature;controlling the time-varying magnetic field generated by said magneticfield generator on the basis of said comparison.
 15. System according toclaim 14, comprising four implants.
 16. Method for treating atrialfibrillation by multiple ablation of the inner walls of a pulmonary veinvia heating, comprising the steps of: implanting one or more implantsaccording to claim 1 in one or more pulmonary veins; applying atime-varying magnetic field at the position of said implants, therebyheating up said one or more implants to a pre-determined ablationtemperature.
 17. Method for treating atrial fibrillation by multipleablation of the inner walls of a pulmonary vein via heating, comprisingthe steps of: implanting one or more implants according to claim 12 inone or more pulmonary veins; applying a time-varying magnetic field atthe position of said implants, thereby heating up said one or moreimplants to a pre-determined ablation temperature.